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 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 study the value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease (HFMD). Methods:76 children diagnosed with ...Objective:To study the value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease (HFMD). Methods:76 children diagnosed with hand, foot and mouth disease in our hospital between May 2013 and March 2016 were selected as the HFMD group of the research, 80 healthy children receiving physical examination in our hospital during the same period were selected as the control group of the research, and the serum was collected to determine the levels of pattern recognition receptors, immunoglobulins, complements, inflammatory media and target organ damage indexes. Results:Serum Collectin, Dectin and CD14 levels of HFMD group were significantly higher than those of control group (P<0.05);serum immunoglobulin G (IgG) IgM, IgA, C3 and C4 levels of HFMD group were significantly lower than those of control group (P<0.05) and negatively correlated with Collectin, Dectin and CD14 levels;serum PCT, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α(TNF-α), N-terminal pro-brain natriuretic peptide (NT-proBNP), neuron-specific enolase (NSE), S100βand surfactant protein A (SP-A) levels of HFMD group were significantly higher than those of control group (P<0.05) and positively correlated with Collectin, Dectin and CD14 levels. Conclusions:High expression of serum pattern recognition receptors Collectin, Dectin and CD14 in children with hand, foot and mouth disease is closely related to the immune response, inflammatory response and target organ function damage during the disease progression.展开更多
Toll-like receptors (TLRs) are found on the membranes of pattern recognition receptors and not only play important roles in activating immune responses but are also involved in the pathogenesis of inflammatory disease...Toll-like receptors (TLRs) are found on the membranes of pattern recognition receptors and not only play important roles in activating immune responses but are also involved in the pathogenesis of inflammatory disease, injury and cancer. Furthermore, TLRs are also able to recognize endogenous alarmins released by damaged tissue and necrosis and/or apoptotic cells and are present in numerous autoimmune diseases. Therefore, the release of endogenous TLR ligands plays an important role in initiating and driving inflammatory diseases. Increasing data suggest a role for TLR signaling in rheumatoid arthritis, which is an autoimmune disease. Although their involvement is not comprehensively understood, the TLRs signaling transducers may provide potential therapeutic targets.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
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
Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components i...Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.展开更多
Pathogen/microbe-associated molecular patterns(PAMPs/MAMPs) are recognized by plant pattern recognition receptors(PRRs)localized on the cell surface to activate immune responses.This PAMP-triggered immunity(PTI) confe...Pathogen/microbe-associated molecular patterns(PAMPs/MAMPs) are recognized by plant pattern recognition receptors(PRRs)localized on the cell surface to activate immune responses.This PAMP-triggered immunity(PTI) confers resistance to a broad range of pathogenic microbes and,therefore,has a great potential for genetically engineering broad-spectrum resistance by transferring PRRs across plant families.Pathogenic effectors secreted by phytopathogens often directly target and inhibit key components of PTI signaling pathways via diverse biochemical mechanisms.In some cases,plants have evolved to produce decoy proteins that mimic the direct virulence target,which senses the biochemical activities of pathogenic effectors.This kind of perception traps the effectors of erroneous targeting and results in the activation of effector-triggered immunity(ETI) instead of suppressing PTI.This mechanism suggests that artificially designed decoy proteins could be used to generate new recognition specificities in a particular plant.In this review,we summarize recent advances in research investigating PAMP recognition by PRRs and virulence effector surveillance by decoy proteins.Successful expansion of recognition specificities,conferred by the transgenic expression of EF-Tu receptor(EFR) and AvrPphB susceptible 1(PBS1) decoys,has highlighted the considerable potential of PRRs and artificially designed decoys to expand plant resistance spectra and the need to further identify novel PRRs and decoys.展开更多
Diabetic nephropathy(DN)is currently the most common complication of diabetes.It is considered to be one of the leading causes of end-stage renal disease(ESRD)and affects many diabetic patients.The pathogenesis of DN ...Diabetic nephropathy(DN)is currently the most common complication of diabetes.It is considered to be one of the leading causes of end-stage renal disease(ESRD)and affects many diabetic patients.The pathogenesis of DN is extremely complex and has not yet been clarified;however,in recent years,increasing evidence has shown the important role of innate immunity in DN pathogenesis.Pattern recognition receptors(PRRs)are important components of the innate immune system and have a significant impact on the occurrence and development of DN.In this review,we classify PRRs into secretory,endocytic,and signal transduction PRRs according to the relationship between the PRRs and subcellular compartments.PRRs can recognize related pathogen-associated molecular patterns(PAMPs)and danger-associated molecular patterns(DAMPs),thus triggering a series of inflammatory responses,promoting renal fibrosis,and finally causing renal impairment.In this review,we describe the proposed role of each type of PRRs in the development and progression of DN.展开更多
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 study the value of serum pattern recognition receptors Collectin, Dectin and CD14 detection for disease evaluation in children with hand, foot and mouth disease (HFMD). Methods:76 children diagnosed with hand, foot and mouth disease in our hospital between May 2013 and March 2016 were selected as the HFMD group of the research, 80 healthy children receiving physical examination in our hospital during the same period were selected as the control group of the research, and the serum was collected to determine the levels of pattern recognition receptors, immunoglobulins, complements, inflammatory media and target organ damage indexes. Results:Serum Collectin, Dectin and CD14 levels of HFMD group were significantly higher than those of control group (P<0.05);serum immunoglobulin G (IgG) IgM, IgA, C3 and C4 levels of HFMD group were significantly lower than those of control group (P<0.05) and negatively correlated with Collectin, Dectin and CD14 levels;serum PCT, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-α(TNF-α), N-terminal pro-brain natriuretic peptide (NT-proBNP), neuron-specific enolase (NSE), S100βand surfactant protein A (SP-A) levels of HFMD group were significantly higher than those of control group (P<0.05) and positively correlated with Collectin, Dectin and CD14 levels. Conclusions:High expression of serum pattern recognition receptors Collectin, Dectin and CD14 in children with hand, foot and mouth disease is closely related to the immune response, inflammatory response and target organ function damage during the disease progression.
基金Supported by The National Natural Science Foundation of China (30871193, 30972748, 81001319)the Natural Science Foundation of Colleges and Universities in Jiangsu Province(Grant No. 09KJB310001)Innovation Fund for Candidate of Doctor in Jiangsu Province(Grant No.CX09B_217Z)
文摘Toll-like receptors (TLRs) are found on the membranes of pattern recognition receptors and not only play important roles in activating immune responses but are also involved in the pathogenesis of inflammatory disease, injury and cancer. Furthermore, TLRs are also able to recognize endogenous alarmins released by damaged tissue and necrosis and/or apoptotic cells and are present in numerous autoimmune diseases. Therefore, the release of endogenous TLR ligands plays an important role in initiating and driving inflammatory diseases. Increasing data suggest a role for TLR signaling in rheumatoid arthritis, which is an autoimmune disease. Although their involvement is not comprehensively understood, the TLRs signaling transducers may provide potential therapeutic targets.
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 the National Natural Science Foundation of China(31372190)
文摘Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB11020600)National Natural Science Foundation of China(31571968,31300234)the Youth Innovation Promotion Association of the Chinese Academy of Sciences
文摘Pathogen/microbe-associated molecular patterns(PAMPs/MAMPs) are recognized by plant pattern recognition receptors(PRRs)localized on the cell surface to activate immune responses.This PAMP-triggered immunity(PTI) confers resistance to a broad range of pathogenic microbes and,therefore,has a great potential for genetically engineering broad-spectrum resistance by transferring PRRs across plant families.Pathogenic effectors secreted by phytopathogens often directly target and inhibit key components of PTI signaling pathways via diverse biochemical mechanisms.In some cases,plants have evolved to produce decoy proteins that mimic the direct virulence target,which senses the biochemical activities of pathogenic effectors.This kind of perception traps the effectors of erroneous targeting and results in the activation of effector-triggered immunity(ETI) instead of suppressing PTI.This mechanism suggests that artificially designed decoy proteins could be used to generate new recognition specificities in a particular plant.In this review,we summarize recent advances in research investigating PAMP recognition by PRRs and virulence effector surveillance by decoy proteins.Successful expansion of recognition specificities,conferred by the transgenic expression of EF-Tu receptor(EFR) and AvrPphB susceptible 1(PBS1) decoys,has highlighted the considerable potential of PRRs and artificially designed decoys to expand plant resistance spectra and the need to further identify novel PRRs and decoys.
基金Project supported by the National Natural Science Foundation of China(Nos.81060063 and 81660129).
文摘Diabetic nephropathy(DN)is currently the most common complication of diabetes.It is considered to be one of the leading causes of end-stage renal disease(ESRD)and affects many diabetic patients.The pathogenesis of DN is extremely complex and has not yet been clarified;however,in recent years,increasing evidence has shown the important role of innate immunity in DN pathogenesis.Pattern recognition receptors(PRRs)are important components of the innate immune system and have a significant impact on the occurrence and development of DN.In this review,we classify PRRs into secretory,endocytic,and signal transduction PRRs according to the relationship between the PRRs and subcellular compartments.PRRs can recognize related pathogen-associated molecular patterns(PAMPs)and danger-associated molecular patterns(DAMPs),thus triggering a series of inflammatory responses,promoting renal fibrosis,and finally causing renal impairment.In this review,we describe the proposed role of each type of PRRs in the development and progression of DN.