Pattern recognition receptor(PRR)is a kind of sensor which is mainly expressed on the surface of innate immune cells.It can recognize pathogen related molecular patterns(PAMPs)or damage related molecular patterns(DAMP...Pattern recognition receptor(PRR)is a kind of sensor which is mainly expressed on the surface of innate immune cells.It can recognize pathogen related molecular patterns(PAMPs)or damage related molecular patterns(DAMPs).The innate immune system uses pattern recognition receptors to recognize pathogenic microorganisms in periodontal tissues and transmit signals to downstream pathways in time,thus triggering immune responses and then eliminating them.PRR has many family members,including toll like receptor family(TLRs),C-type lectin receptor family(CLRs),retinoic acid induced gene I(RIG-I)like receptor family(RLRs)and nucleotide binding oligomer domain(NOD)like receptor family(NLRs).Among them,RLRs are cytoplasmic receptors that recognize dsRNA from RNA viruses and have little association with chronic periodontitis.In this paper,the classification and structure of TLRs,CLRs,NLRs and the role of signal transduction pathway in chronic periodontitis are reviewed.In order to enrich the pathogenesis of periodontitis,provide new ideas for the treatment and prevention of chronic periodontitis.展开更多
Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR...Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.展开更多
Pattern recognition receptors (PRRs) and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate inv...Pattern recognition receptors (PRRs) and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms.展开更多
Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells...Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.展开更多
Citrus canker, an epidemic quarantine disease caused by Xanthomonas axonopodis pv. citri, has brought a great damage in citrus production worldwide. Herein, a rice PRR (pattern recognition receptor) gene Xa21 togeth...Citrus canker, an epidemic quarantine disease caused by Xanthomonas axonopodis pv. citri, has brought a great damage in citrus production worldwide. Herein, a rice PRR (pattern recognition receptor) gene Xa21 together with GUS reporter gene and hygromycin phosphotransferase gene (HPT) was introduced into Anliucheng sweet orange (Citrus sinensis Osbeck) via Agrobacterium-mediated transformation of embryogenic callus. The transgenic calluses were screened on MT basal medium containing hygromycin (HYG) and detected by histochemical GUS staining. The transgenic plantlets were recovered through somatic embryogenesis pathway. The regenerated plantlets were accustomed to and maintained in the greenhouse. The transgene integration of recovered plantlets was identiifed by PCR and Southern blot hybridization. It showed that all the transgenic plantlets tested had undergone single copy integration, the expression of Xa21 in eight different transgenic lines detected by qRT-PCR can be divided into three grades, high for T5 and T6, middle for T4 and low for the rest. The tolerance to citrus canker disease of the three recovered transgenic lines T2, T4 and T6 was assessed by in vitro pin-puncture inoculation. The results showed that all the three transgenic lines conferred improved resistance to citrus canker bacterium infection and the T4 transgenic line displayed the highest resistance. The mechanism and feasibility of rice Xa21 in triggering innate immunity in citrus was brielfy discussed.展开更多
C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity ...C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity in insects.In this study,we report a novel dual carbohydrate-recognition domain(CRD)CTL from Plutella xylostella which we designate PxIML.PxIML is a protein with a 969 bp open reading frame(ORF)encoding 322 amino acids,containing a signal peptide and a dual-CRD with EPN(Glu_(124)-Pro_(125)-Asn_(126))and QPD(Gln_(274)-Pro_(275)-Asp_(276))motifs.The expression of PxIML mRNA in the fat body was significantly higher than in hemocytes and midgut.The relative expression levels of PxIML in the whole insect and the fat body were significantly inhibited after infection with Bacillus thuringiensis 8010(Bt8010)at 18 h,while they were significantly upregulated after infection with Serratia marcescens IAE6 or Pichia pastoris.The recombinant PxIML(rPxIML)protein could bind to the tested pathogen-associated molecular patterns(PAMPs),and the bacteria of Enterobacter sp.IAE5,S.marcescens IAE6,Staphylococcus aureus,Escherichia coli BL21,and Bt8010 in a Ca^(2+)-dependent manner,however,it showed limited binding to the fungus,P.pastoris.The rPxIML exhibited strong activity in the presence of Ca^(2+) to agglutinate Bt8010,Enterobacter sp.IAE5 and S.aureus,but it only weakly agglutinated with E.coli BL21,and could not agglutinate with S.marcescens IAE6 or P.pastoris.Furthermore,the rPxIML could bind to hemocytes,promote the adsorption of hemocytes to beads,and enhance the phenoloxidase(PO)activity and melanization of P.xylostella.Our results suggest that PxIML plays an important role in pathogen recognition and in mediating subsequent humoral and cellular immunity of P.xylostella.展开更多
Crohn’s disease(CD)is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines.These pro-inflammatory cytokines are produced by macrophages and dendritic cells(D...Crohn’s disease(CD)is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines.These pro-inflammatory cytokines are produced by macrophages and dendritic cells(DCs)upon sensing the intestinal microbiota by the pattern recognition receptors(PRRs).Impaired activation of PRR-mediated signaling pathways is associated with chronic gastrointestinal inflammation,as shown by the fact that loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene increase the risk of CD development.Autophagy is an intracellular degradation process,during which cytoplasmic nutrients and intracellular pathogens are digested.Given that impaired reaction to intestinal microbiota alters signaling pathways mediated by PRRs,it is likely that dysfunction of the autophagic machinery is involved in the development of CD.Indeed,the loss-of-function mutation T300A in the autophagy related 16 like 1(ATG16L1)protein,a critical regulator of autophagy,increases susceptibility to CD.Recent studies have provided evidence that ATG16L1 is involved not only in autophagy,but also in PRR-mediated signaling pathways.ATG16L1 negatively regulates pro-inflammatory cytokine responses of macrophages and DCs after these cells sense the intestinal microbiota by PRRs.Here,we discuss the molecular mechanisms underlying the development of CD in the T300A ATG16L1 mutation by focusing on PRR-mediated signaling pathways.展开更多
Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemi...Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities.However,the pathogenesis of FK,especially the immunologic mechanism within it,has not yet been deeply clarified.A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis.Meanwhile,the immune protection strategies are also urgently required to manage FK.This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK,in hope of providing valuable reference information for more effective anti-fungal treatment.展开更多
During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like recept...During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.展开更多
Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).Thi...Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.展开更多
Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be al...Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues.These wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress perception.Plant cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease resistance.Similarly,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI responses.The number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent years.However,the structural mechanisms underlying glycan recognition by plant PRRs remain limited.Currently,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological responses.Nevertheless,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide recognition.These include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and LRR-extensins.The characterization of structural basis of glycans recognition by these new plant receptors will shed light on their similarities with those of mammalians involved in glycan perception.The gained knowledge holds the potential to facilitate the development of sustainable,glycan-based crop protection solutions.展开更多
Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by...Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns (PAMPs)-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.展开更多
The gut microbiota plays a key role in host health and disease,particularly through their interactions with the immune system.Intestinal homeostasis is dependent on the symbiotic relationships between the host and the...The gut microbiota plays a key role in host health and disease,particularly through their interactions with the immune system.Intestinal homeostasis is dependent on the symbiotic relationships between the host and the diverse gut microbiota,which is influenced by the highly co-evolved immune-microbiota interactions.The first step of the interaction between the host and the gut microbiota is the sensing of the gut microbes by the host immune system.In this review,we describe the cells of the host immune system and the proteins that sense the components and metabolites of the gut microbes.We further highlight the essential roles of pattern recognition receptors(PRRs),the G protein-coupled receptors(GPCRs),aryl hydrocarbon receptor(AHR)and the nuclear receptors expressed in the intestinal epithelial cells(IECs)and the intestine-resident immune cells.We also discuss the mechanisms by which the disruption of microbial sensing because of genetic or environmental factors causes human diseases such as the inflammatory bowel disease(IBD).展开更多
Background: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is ...Background: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. Methods: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human β-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-riB (NF-KB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. Results: The relative expression of SP-D in adenoidal epithelium ofpCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ±0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. Conclusions: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process ofpCRS.展开更多
Background Trichophyton rubrum (T. rubrum) represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested tha...Background Trichophyton rubrum (T. rubrum) represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested that it may result from the failure of epithelial cells to recognize T. rubrum effectively and initiate effective immune responses. The C-type lectin receptors (CLR) and toll-like receptors (TLR) are the two major pattern recognition receptors (PRRs) that recognize fungal components. Therefore, the purpose of the study was to analyze the expression of those PRRs and the cytokines in HaCaT cells stimulated with heat-inactivated T. rubrum conidia and hyphae, respectively. Methods HaCaT cells were unstimulated or stimulated with heat-inactivated T. rubrum conidia and hyphae (l×106 and 1.5×105 colony-forming unit (CFU) in 2 ml medium, respectively) for 6, 12 and 24 hours. The mRNA expression of PRRs involved in recognizing fungal pathogen-associated molecular patterns (PAMPs) and signaling molecules were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, surface toll-like receptor (TLR) 2, TLR4 and Dectin-1 were analyzed by fluorescence-activated cell sorter (FACS) 24 hours after treatment. The cytokines were detected in cell culture supernatants of HaCaT cells in 12 and 24 hours after treatment. Results HaCaT cells constitutively expressed mRNA of membrane-bound TLR1,2, 4 and 6, Dectinl and DC-SIGN, but not Dectin-2 or Mincle. Heat-killed T. rubrum did not significantly upregulate gene transcriptions of the PRRs of HaCaT cells. Heat-inactivated T. rubrum conidia significantly reduced the surface expression of TLR2 and Dectin-1, and suppressed the secretions of interferon-inducible protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) of HaCaT cells, while heat-killed T. rubrum hyphae significantly induced the secretions of IP-10 and MCP-I. Conclusion The cell-wall antigens of T. rubrum fail to activate transcriptional expression of PRRs and induce a lower immune response of HaCaT cells by limited cytokines secretion.展开更多
Background: Trichophyton rubrum is superficial fungi characteristically confined to dead keratinized tissues. These observations suggest that the soluble components released by the fungus could influence the host imm...Background: Trichophyton rubrum is superficial fungi characteristically confined to dead keratinized tissues. These observations suggest that the soluble components released by the fungus could influence the host immune response in a cell in contact-free manner. Therefore, this research aimed to analyze whether the culture supernatant derived from T. rubrum grown in the nail medium could elicit the immune response of keratinocyte effectively. Methods: The culture supernatants of two strains (T1a, TXHB) were compared for the β-glucan concentrations and their capacity to impact the innate immunity of keratinocytes. The β-glucan concentrations in the supernatants were determined with the fungal G-test kit and protein concentrations with bicinchoninic acid protein quantitative method, then HaCaT was stimulated with different concentrations of culture supernatants by adopting morphological method to select a suitable dosage. Expressions of host defense genes were assessed by quantitative polymerase chain reaction after the HaCaT was stimulated with the culture supernatants. Data were analyzed with one-way analysis of variance, followed by the least significant difference test. Results: The T. rubrum strains (T1a and TXHB) released β-glucan of 87.530 ± 37.581 pg/ml and 15.747 ± 6.453 pg/ml, respectively into the media. The messenger RNA (mRNA) expressions of toll-like receptor-2 (TLR2), TLR4, and CARD9 were moderately up-regulated in HaCaT within 6-h applications of both supernatants. HaCaT cells were more responsive to Tla than TXHB. The slight increase of dendritic cells-specific intercellular adhesion molecule 3-grabbing nonintegrin expression was faster and stronger, induced by T1a supematant than TXHB. The moderate decreases of RNase 7, the slight up-regulations of Dectin-1 and interleukin-8 at the mRNA level were detected only in response to T la rather than TXHB After a long-time contact, all the elevated defense genes decreased alter 24 h. Conclusion: The culture supernatant of T. rubrum could directly and transiently activate the innate immune response of keratinocytes.展开更多
The rice pattern recognition receptor (PRR) XA21 confers race-specific resistance in leaf infection by bacterial blight Xathornonas oryzae pv. oryzae (Xoo), and was shown to be primarily localized to the endoplasm...The rice pattern recognition receptor (PRR) XA21 confers race-specific resistance in leaf infection by bacterial blight Xathornonas oryzae pv. oryzae (Xoo), and was shown to be primarily localized to the endoplasmic reticulum (ER) when expressed with its native promoter or overexpressed in the protoplast. However, whether the protein is still ER- localization in the intact cell when overexpressed remains to be identified. Here, we showed that XA21, its kinase-dead mutant XA21PK736EP and the triple autophosphorylation mutant XA21PS686AJT688AJS699A GFP fusions were primarily localized to the plasma membrane (PM) when overexpressed in the intact transgenic rice cell, and also localized to the ER in the transgenic protoplast. The transgenic plants constitutively expressing the wild-type XA21 or its GFP fusion displayed racespecific resistance to Xoo at the adult and seedling stages. XA21 and XA21PK736EP could be internalized probably via the SCAMP-positive early endosomal compartment in the protoplast, suggesting that XA21 might be endocytosed to initiate resistance responses during pathogen infection. We also established a root infection system and demonstrated that XA21 also mediated race-specific resistance responses to Xoo in the root. Our current study provides an insight into the nature of the XA21-mediated resistance and a practical approach using the root cell system to further dissect the cellular signaling of the PRR during the rice-Xoo interaction.展开更多
Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of ...Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.展开更多
The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifically recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrate...The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifically recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrated that Arabidopsis EFR confers broad-spectrum bacterial resistance in the EFR transgenic solanaceous plants. Here, the transgenic rice plants (Oryza sativa L. ssp. japonica cv. Zhonghua 17) and cell cultures with constitutive expression of AtEFR were developed to investigate whether AtEFR senses EF-Tu and thus enhances bacterial resistance in the monocot plants. We'demonstrated that the Xanthomonas oryzae-derived elf18 peptide induced oxidative burst and mitogen-activated protein kinase activa- tion in the AtEFR transgenic rice cells and plants, respectively. Pathogenesis-related genes, such as OsPBZ1, were upregulated dramatically in transgenic rice plant and cell lines in response to elf18 stimulation. Importantly, pretreatment with elf18 trig- gered strong resistance to X. oryzae pv. oryzae in the transgenic plants, which was largely dependent on the AtEFR expressionlevel. These plants also exhibited enhanced resistance to rice bacterial brown stripe, but not to rice fungal blast. Collectively, the results indicate that the rice plants with heterologous expression of AtEFR recognize bacterial EF-Tu and exhibit enhanced broad-spectrum bacterial disease resistance and that pattern recognition receptor-mediated immunity may be manipulated across the two plant classes, dicots and monocots.展开更多
基金Scientific research project of Hainan Provincial Department of Education(No.hnky2018zd-7)。
文摘Pattern recognition receptor(PRR)is a kind of sensor which is mainly expressed on the surface of innate immune cells.It can recognize pathogen related molecular patterns(PAMPs)or damage related molecular patterns(DAMPs).The innate immune system uses pattern recognition receptors to recognize pathogenic microorganisms in periodontal tissues and transmit signals to downstream pathways in time,thus triggering immune responses and then eliminating them.PRR has many family members,including toll like receptor family(TLRs),C-type lectin receptor family(CLRs),retinoic acid induced gene I(RIG-I)like receptor family(RLRs)and nucleotide binding oligomer domain(NOD)like receptor family(NLRs).Among them,RLRs are cytoplasmic receptors that recognize dsRNA from RNA viruses and have little association with chronic periodontitis.In this paper,the classification and structure of TLRs,CLRs,NLRs and the role of signal transduction pathway in chronic periodontitis are reviewed.In order to enrich the pathogenesis of periodontitis,provide new ideas for the treatment and prevention of chronic periodontitis.
文摘Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.
基金ACKNOWLEDGEMENTS TJ is supported by the Fundamental Research Funds for the Central Universities and the 100 Talents Program of the Chinese Academy of Sciences. YIL is supported by the China Postdoctoral Science Foundation. We express our appreciation to Tsan Sam Xiao at Case Western Reserve University and Bin Lin at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA for proofreading and suggestions.
文摘Pattern recognition receptors (PRRs) and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms.
基金supported by a National Institutes of Health grant (No. R01AI132526)a UConn Health Startup fund to Wang P。
文摘Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.
基金financially supported by the National HighTech R&D Program of China (863, 2011AA100205)the National Natural Science Foundation of China (31125024)
文摘Citrus canker, an epidemic quarantine disease caused by Xanthomonas axonopodis pv. citri, has brought a great damage in citrus production worldwide. Herein, a rice PRR (pattern recognition receptor) gene Xa21 together with GUS reporter gene and hygromycin phosphotransferase gene (HPT) was introduced into Anliucheng sweet orange (Citrus sinensis Osbeck) via Agrobacterium-mediated transformation of embryogenic callus. The transgenic calluses were screened on MT basal medium containing hygromycin (HYG) and detected by histochemical GUS staining. The transgenic plantlets were recovered through somatic embryogenesis pathway. The regenerated plantlets were accustomed to and maintained in the greenhouse. The transgene integration of recovered plantlets was identiifed by PCR and Southern blot hybridization. It showed that all the transgenic plantlets tested had undergone single copy integration, the expression of Xa21 in eight different transgenic lines detected by qRT-PCR can be divided into three grades, high for T5 and T6, middle for T4 and low for the rest. The tolerance to citrus canker disease of the three recovered transgenic lines T2, T4 and T6 was assessed by in vitro pin-puncture inoculation. The results showed that all the three transgenic lines conferred improved resistance to citrus canker bacterium infection and the T4 transgenic line displayed the highest resistance. The mechanism and feasibility of rice Xa21 in triggering innate immunity in citrus was brielfy discussed.
基金the project of the National Key R&D Program of China(2017YFE0122000)the National Natural Science Foundation of China(31871968)the Natural Science Foundation of Fujian Province,China(2018J01614).
文摘C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity in insects.In this study,we report a novel dual carbohydrate-recognition domain(CRD)CTL from Plutella xylostella which we designate PxIML.PxIML is a protein with a 969 bp open reading frame(ORF)encoding 322 amino acids,containing a signal peptide and a dual-CRD with EPN(Glu_(124)-Pro_(125)-Asn_(126))and QPD(Gln_(274)-Pro_(275)-Asp_(276))motifs.The expression of PxIML mRNA in the fat body was significantly higher than in hemocytes and midgut.The relative expression levels of PxIML in the whole insect and the fat body were significantly inhibited after infection with Bacillus thuringiensis 8010(Bt8010)at 18 h,while they were significantly upregulated after infection with Serratia marcescens IAE6 or Pichia pastoris.The recombinant PxIML(rPxIML)protein could bind to the tested pathogen-associated molecular patterns(PAMPs),and the bacteria of Enterobacter sp.IAE5,S.marcescens IAE6,Staphylococcus aureus,Escherichia coli BL21,and Bt8010 in a Ca^(2+)-dependent manner,however,it showed limited binding to the fungus,P.pastoris.The rPxIML exhibited strong activity in the presence of Ca^(2+) to agglutinate Bt8010,Enterobacter sp.IAE5 and S.aureus,but it only weakly agglutinated with E.coli BL21,and could not agglutinate with S.marcescens IAE6 or P.pastoris.Furthermore,the rPxIML could bind to hemocytes,promote the adsorption of hemocytes to beads,and enhance the phenoloxidase(PO)activity and melanization of P.xylostella.Our results suggest that PxIML plays an important role in pathogen recognition and in mediating subsequent humoral and cellular immunity of P.xylostella.
文摘Crohn’s disease(CD)is driven by the loss of tolerance to intestinal microbiota and excessive production of pro-inflammatory cytokines.These pro-inflammatory cytokines are produced by macrophages and dendritic cells(DCs)upon sensing the intestinal microbiota by the pattern recognition receptors(PRRs).Impaired activation of PRR-mediated signaling pathways is associated with chronic gastrointestinal inflammation,as shown by the fact that loss-of-function mutations in the nucleotide-binding oligomerization domain 2 gene increase the risk of CD development.Autophagy is an intracellular degradation process,during which cytoplasmic nutrients and intracellular pathogens are digested.Given that impaired reaction to intestinal microbiota alters signaling pathways mediated by PRRs,it is likely that dysfunction of the autophagic machinery is involved in the development of CD.Indeed,the loss-of-function mutation T300A in the autophagy related 16 like 1(ATG16L1)protein,a critical regulator of autophagy,increases susceptibility to CD.Recent studies have provided evidence that ATG16L1 is involved not only in autophagy,but also in PRR-mediated signaling pathways.ATG16L1 negatively regulates pro-inflammatory cytokine responses of macrophages and DCs after these cells sense the intestinal microbiota by PRRs.Here,we discuss the molecular mechanisms underlying the development of CD in the T300A ATG16L1 mutation by focusing on PRR-mediated signaling pathways.
基金Supported by the Natural Science Foundation of Tianjin(No.19JCYBJC25700)Clinical Key Discipline(Specialty)Construction Project of Tianjin(No.TJLCZDXKM002)+1 种基金Science and Technology Projects of Social Development of Tianjin Binhai New District(No.BHXQKJXM-SF-2018-05)Science and Technology Projects of Health Commission of Tianjin Binhai New District(No.2019BWKZ008)。
文摘Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities.However,the pathogenesis of FK,especially the immunologic mechanism within it,has not yet been deeply clarified.A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis.Meanwhile,the immune protection strategies are also urgently required to manage FK.This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK,in hope of providing valuable reference information for more effective anti-fungal treatment.
文摘During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.
基金This study was supported by the National Natural Science Foundation of China(No.81872000).
文摘Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.
基金supported by grant PID2021-126006OB-I00 to A.M.and L.J.grant PID20220-113588RB-I00 to S.M.-S+6 种基金funded by MCIN/AEI/10.13039/501100011033by ERDF A way of making Europe.D.J.B.supported by PRE2019-091276 and P.F.-C.by postdoctoral fellowships financially supported by the Severo Ochoa Program for Centres of Excellence in R&D(grants SEV-2016-0672 and CEX2020-000999-S)funded by MCIN/AEI/10.13039/501100011033.M.M.-D.was recipient of PhD fellow(PRE2019-08812)funded by MCIN/AEI/10.13039/501100011033.E.G.-Rwas supported by Autonomous Region of Madrid fellowship(S2017/BMD-3673)the European Commission-Next Generation EU(Regulation EU2020/2094)through CSIC’s Global Health Platform PTI Salud Global.
文摘Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues.These wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress perception.Plant cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease resistance.Similarly,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI responses.The number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent years.However,the structural mechanisms underlying glycan recognition by plant PRRs remain limited.Currently,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological responses.Nevertheless,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide recognition.These include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and LRR-extensins.The characterization of structural basis of glycans recognition by these new plant receptors will shed light on their similarities with those of mammalians involved in glycan perception.The gained knowledge holds the potential to facilitate the development of sustainable,glycan-based crop protection solutions.
文摘Apoptosis inhibitor of macrophages (AIMs), a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily (SRCR-SF). This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM (rAIM) expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor (TLR) ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns (PAMPs)-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.
基金We would like to thank W.Tao,H.Ma,and other members of Zhu laboratory and Z.Wei in Richard Flavell’s lab for helpful discussions.This work was supported by grants from the National Key R&D Program of China(Grant No.2018YFA0508000,S.Z.)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB29030101,S.Z.)+1 种基金the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-074,S.Z.)the National Natural Science Foundation of China(Grant No.82061148013,S.Z.).
文摘The gut microbiota plays a key role in host health and disease,particularly through their interactions with the immune system.Intestinal homeostasis is dependent on the symbiotic relationships between the host and the diverse gut microbiota,which is influenced by the highly co-evolved immune-microbiota interactions.The first step of the interaction between the host and the gut microbiota is the sensing of the gut microbes by the host immune system.In this review,we describe the cells of the host immune system and the proteins that sense the components and metabolites of the gut microbes.We further highlight the essential roles of pattern recognition receptors(PRRs),the G protein-coupled receptors(GPCRs),aryl hydrocarbon receptor(AHR)and the nuclear receptors expressed in the intestinal epithelial cells(IECs)and the intestine-resident immune cells.We also discuss the mechanisms by which the disruption of microbial sensing because of genetic or environmental factors causes human diseases such as the inflammatory bowel disease(IBD).
文摘Background: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. Methods: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human β-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-riB (NF-KB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. Results: The relative expression of SP-D in adenoidal epithelium ofpCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ±0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. Conclusions: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process ofpCRS.
基金This Work was supported by the grants from theFundamental Research Funds for the Central Universities (No. 10ykpy04) and the National Natural Science Foundation of China (No. 30600028).
文摘Background Trichophyton rubrum (T. rubrum) represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested that it may result from the failure of epithelial cells to recognize T. rubrum effectively and initiate effective immune responses. The C-type lectin receptors (CLR) and toll-like receptors (TLR) are the two major pattern recognition receptors (PRRs) that recognize fungal components. Therefore, the purpose of the study was to analyze the expression of those PRRs and the cytokines in HaCaT cells stimulated with heat-inactivated T. rubrum conidia and hyphae, respectively. Methods HaCaT cells were unstimulated or stimulated with heat-inactivated T. rubrum conidia and hyphae (l×106 and 1.5×105 colony-forming unit (CFU) in 2 ml medium, respectively) for 6, 12 and 24 hours. The mRNA expression of PRRs involved in recognizing fungal pathogen-associated molecular patterns (PAMPs) and signaling molecules were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, surface toll-like receptor (TLR) 2, TLR4 and Dectin-1 were analyzed by fluorescence-activated cell sorter (FACS) 24 hours after treatment. The cytokines were detected in cell culture supernatants of HaCaT cells in 12 and 24 hours after treatment. Results HaCaT cells constitutively expressed mRNA of membrane-bound TLR1,2, 4 and 6, Dectinl and DC-SIGN, but not Dectin-2 or Mincle. Heat-killed T. rubrum did not significantly upregulate gene transcriptions of the PRRs of HaCaT cells. Heat-inactivated T. rubrum conidia significantly reduced the surface expression of TLR2 and Dectin-1, and suppressed the secretions of interferon-inducible protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) of HaCaT cells, while heat-killed T. rubrum hyphae significantly induced the secretions of IP-10 and MCP-I. Conclusion The cell-wall antigens of T. rubrum fail to activate transcriptional expression of PRRs and induce a lower immune response of HaCaT cells by limited cytokines secretion.
文摘Background: Trichophyton rubrum is superficial fungi characteristically confined to dead keratinized tissues. These observations suggest that the soluble components released by the fungus could influence the host immune response in a cell in contact-free manner. Therefore, this research aimed to analyze whether the culture supernatant derived from T. rubrum grown in the nail medium could elicit the immune response of keratinocyte effectively. Methods: The culture supernatants of two strains (T1a, TXHB) were compared for the β-glucan concentrations and their capacity to impact the innate immunity of keratinocytes. The β-glucan concentrations in the supernatants were determined with the fungal G-test kit and protein concentrations with bicinchoninic acid protein quantitative method, then HaCaT was stimulated with different concentrations of culture supernatants by adopting morphological method to select a suitable dosage. Expressions of host defense genes were assessed by quantitative polymerase chain reaction after the HaCaT was stimulated with the culture supernatants. Data were analyzed with one-way analysis of variance, followed by the least significant difference test. Results: The T. rubrum strains (T1a and TXHB) released β-glucan of 87.530 ± 37.581 pg/ml and 15.747 ± 6.453 pg/ml, respectively into the media. The messenger RNA (mRNA) expressions of toll-like receptor-2 (TLR2), TLR4, and CARD9 were moderately up-regulated in HaCaT within 6-h applications of both supernatants. HaCaT cells were more responsive to Tla than TXHB. The slight increase of dendritic cells-specific intercellular adhesion molecule 3-grabbing nonintegrin expression was faster and stronger, induced by T1a supematant than TXHB. The moderate decreases of RNase 7, the slight up-regulations of Dectin-1 and interleukin-8 at the mRNA level were detected only in response to T la rather than TXHB After a long-time contact, all the elevated defense genes decreased alter 24 h. Conclusion: The culture supernatant of T. rubrum could directly and transiently activate the innate immune response of keratinocytes.
文摘The rice pattern recognition receptor (PRR) XA21 confers race-specific resistance in leaf infection by bacterial blight Xathornonas oryzae pv. oryzae (Xoo), and was shown to be primarily localized to the endoplasmic reticulum (ER) when expressed with its native promoter or overexpressed in the protoplast. However, whether the protein is still ER- localization in the intact cell when overexpressed remains to be identified. Here, we showed that XA21, its kinase-dead mutant XA21PK736EP and the triple autophosphorylation mutant XA21PS686AJT688AJS699A GFP fusions were primarily localized to the plasma membrane (PM) when overexpressed in the intact transgenic rice cell, and also localized to the ER in the transgenic protoplast. The transgenic plants constitutively expressing the wild-type XA21 or its GFP fusion displayed racespecific resistance to Xoo at the adult and seedling stages. XA21 and XA21PK736EP could be internalized probably via the SCAMP-positive early endosomal compartment in the protoplast, suggesting that XA21 might be endocytosed to initiate resistance responses during pathogen infection. We also established a root infection system and demonstrated that XA21 also mediated race-specific resistance responses to Xoo in the root. Our current study provides an insight into the nature of the XA21-mediated resistance and a practical approach using the root cell system to further dissect the cellular signaling of the PRR during the rice-Xoo interaction.
基金supported by National Natural Science Foundation of China(No.39970340,No.30570865)Natural Science Foundation of Shanghai(No.02ZB14041,No.034119916).
文摘Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.
基金supported by the 973 program 2011CB100700the transgenic crop project 2012ZX08009003+1 种基金the National Natural Science Foundation of China grant 31272007the Key Project in the National Science and Technology Pillar Program 2012BAD19B03 to W.S
文摘The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifically recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrated that Arabidopsis EFR confers broad-spectrum bacterial resistance in the EFR transgenic solanaceous plants. Here, the transgenic rice plants (Oryza sativa L. ssp. japonica cv. Zhonghua 17) and cell cultures with constitutive expression of AtEFR were developed to investigate whether AtEFR senses EF-Tu and thus enhances bacterial resistance in the monocot plants. We'demonstrated that the Xanthomonas oryzae-derived elf18 peptide induced oxidative burst and mitogen-activated protein kinase activa- tion in the AtEFR transgenic rice cells and plants, respectively. Pathogenesis-related genes, such as OsPBZ1, were upregulated dramatically in transgenic rice plant and cell lines in response to elf18 stimulation. Importantly, pretreatment with elf18 trig- gered strong resistance to X. oryzae pv. oryzae in the transgenic plants, which was largely dependent on the AtEFR expressionlevel. These plants also exhibited enhanced resistance to rice bacterial brown stripe, but not to rice fungal blast. Collectively, the results indicate that the rice plants with heterologous expression of AtEFR recognize bacterial EF-Tu and exhibit enhanced broad-spectrum bacterial disease resistance and that pattern recognition receptor-mediated immunity may be manipulated across the two plant classes, dicots and monocots.