Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatmen...Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.展开更多
Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.I...Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.In this study,we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs.Dmrt1 recruited promyelocytic leukemia zinc finger(Plzf),also known as zinc finger and BTB domain-containing protein 16(Zbtb16),to repress the Toll-like receptor 4(TLR4)-dependent inflammatory signaling pathway and nuclear factor(NF)-κB.Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells,while the expression of proinflammatory factors were significantly enhanced.We also demonstrated that Dmrt1 stimulated proliferation of mGSCs,but repressed apoptosis caused by the immune response.Thus,Dmrt1 is sufficient to reduce inflammation in the testes,thereby establishing the stability of spermatogenesis and the testicular microenvironment.展开更多
Foot-and-mouth disease virus (FMDV) is highly contagious and responsible for huge outbreaks among cloven hoofed animals. The aim of the present study is to evaluate a plasmid DNA immunization system that expresses t...Foot-and-mouth disease virus (FMDV) is highly contagious and responsible for huge outbreaks among cloven hoofed animals. The aim of the present study is to evaluate a plasmid DNA immunization system that expresses the FMDV/OflRN/2007 VP1 gene and compare it with the conventional inactivated vaccine in an animal model. The VP1 gene was sub-cloned into the unique Kpn I and BamH I cloning sites of the peDNA3.1+ and pEGFP-N1 vectors to construct the VPI gene cassettes. The transfected BHKT7 cells with sub-cloned pEGFP-N1-VP1 vector expressed GFP-VP1 fusion protein and displayed more green fluorescence spots than the transfected BHKT7 cells with pEGFP-N1 vector, which solely expressed the GFP protein. Six mice groups were respectively immunized by the sub-cloned pcDNA3.1+-VP1 gene cassette as the DNA vaccine, DNA vaccine and PCMV-SPORT-GMCSF vector (as molecular adjuvant) together, conventional vaccine, PBS (as negative control), pcDNA3.1+ vector (as control group) and PCMV-SPORT vector that contained the GMCSF gene (as control group). Significant neutralizing antibody responses were induced in the mice which were immunized using plasmid vectors expressing the VP1 and GMCSF genes together, the DNA vaccine alone and the conventional inactivated vaccine (P〈0.05). Co-administration of DNA vaccine and GMCSF gene improved neutralizing antibody response in comparison with administration of the DNA vaccine alone, but this response was the most for the conventional vaccine group. However, induction of humeral immunity response in the conventional vaccine group was more protective than for the DNA vaccine, but T-cell proliferation and IFN-? concentration were the most in DNA vaccine with the GMCSF gene. Therefore the group that was vaccinated by DNA vaccine with the GMCSF gene, showed protective neutralizing antibody response and the most Thl cellular immunity.展开更多
Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the ...Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the parasite can exert several immune suppressive mechanisms that facilitate escaping the immune responses.One of these mechanisms is the up-regulation of programmed death-1/programmed death ligand-1 pathway which causes T cells to undergo exhaustion.Autophagy is strongly linked to the immune response,with some research indicating that activating autophagy reduces the immune response to some intracellular pathogens,while others indicate that activating autophagy limits the growth of intracellular pathogens.Leishmania was found to subvert the host defense mechanisms for its own persistence,such as Leishmania-induced autophagy modulation.Leishmania was reported to activate autophagy in different studies,thus getting a dual benefit by evading the immune system and simultaneously utilizing the autophagy byproducts as nutrients.In this review,we introduced different immune evasion/suppressive mechanisms used by Leishmania,and different immunotherapies which were developed accordingly.We focused on the programmed death-1/programmed death ligand-1 pathway as well as autophagy with the potential interplay of both mechanisms.展开更多
Viral protein U (Vpu) is an accessory protein associated with two main functions important in human immu-nodeficiency virus type 1 (HIV-1) replication and dis-semination; these are down-regulation of CD4 receptor ...Viral protein U (Vpu) is an accessory protein associated with two main functions important in human immu-nodeficiency virus type 1 (HIV-1) replication and dis-semination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and en-hancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen inter-action is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo . In order to compre-hensively understand Vpu variability, it is important to integrate at the population level the genetic association approaches to identify specifc amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo . This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune re-sponses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu func-tional implication in HIV-1 pathogenesis.展开更多
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice t...The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6–8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P〈0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P〈0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.展开更多
Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical sig...Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.展开更多
Objective: To study the correlation of IRAK1 and TRAF6 expression with inflammatory response and immune response in oral lichen planus lesions. Methods: Patients who were diagnosed with oral lichen planus in Ziyang Fi...Objective: To study the correlation of IRAK1 and TRAF6 expression with inflammatory response and immune response in oral lichen planus lesions. Methods: Patients who were diagnosed with oral lichen planus in Ziyang First People's Hospital between June 2014 and February 2017 were selected as the OLP group of the study, and the oral lichen planus lesions were collected;42 patients who accepted surgery for oral trauma or maxillofacial plastic surgery were selected as the control group of the study, and the normal oral mucosa tissue was collected. The expression of IRAK1, TRAF6 and TLR4 signaling pathway molecules, Th1/Th2/Treg/Th17 transcription factors and cytokines in tissue samples were detected. Results:IRAK1, TRAF6, TLR4, MyD88 and NF-kB mRNA expression and protein expression in oral lichen planus lesions of OLP patients were significantly lower than those of control group, T-bet and IFN-γ levels were significantly lower than those of control group, and GATA3, FOXP3, RORγt, IL-4, IL-10 and IL-17 levels were significantly higher than those of control group;IRAK1 and TRAF6 expression in oral mucosa tissue were positively correlated with TLR4, MyD88 and NF-kB expression as well as T-bet and IFN-γ levels, and were negatively correlated with GATA3, FOXP3, RORγt, IL-4, IL-10 and IL-17 levels. Conclusion: IRAK1 and TRAF6 expression in oral lichen planus lesions can inhibit the TLR4 inflammatory response pathway and lead to Th1/Th2 /Treg/Th17 immune response disorder.展开更多
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated...Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.展开更多
Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with ast...Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with asthma.We assessed asthma by Asthma Control Test,the lung function by spirometry before and after the bronchodilator test,followed by collecting induced sputum.The next day,we collected exhaled breath condensate(EBC)and conducted a 3-minute isocapnic hyperventilation with cold air(IHCA),followed by collecting spontaneously produced sputum.Results:Group 1 included 20 patients with cold airway hyperresponsiveness(CAHR),and group 2 included 22 patients without CAHR.In both groups,a high level of neutrophils in bronchial secretion was observed before and after IHCA.In response to IHCA,the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γafter IHCA had an inverse relationship(r=-0.60;P=0.017).The baseline IFN-γin EBC before and after IHCA was lower in group 1.Airway response to cold exposure directly correlated with IFN-γlevels after IHCA(Rs=0.42;P=0.014).Conclusion:In asthma patients with CAHR,there is a relationship between the persistence of mixed inflammation and the level of IFN-γin the bronchi.IFN-γin response to IHCA is decreased with increased cytokine utilization during cold bronchospasm,which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells(Th)1 immune response.展开更多
Porcine epidemic diarrhea(PED)caused by the porcine epidemic diarrhea virus(PEDV),is a severe infectious and devastating swine disease that leads to serious economic losses in the swine industry worldwide.An increased...Porcine epidemic diarrhea(PED)caused by the porcine epidemic diarrhea virus(PEDV),is a severe infectious and devastating swine disease that leads to serious economic losses in the swine industry worldwide.An increased number of PED cases caused by variant PEDV have been reported in many countries since 2010.S protein is the main immunogenic protein containing some B-cell epitopes that can induce neutralizing antibodies of PEDV.In this study,the construction,expression and purification of Pseudomonas aeruginosa exotoxin A(PE)without domain Ⅲ(PE△Ⅲ)as a vector was performed for the delivery of PEDV S-A or S-B.PE(△Ⅲ)PEDV S-A and PE(△Ⅲ)PEDV S-B recombinant proteins were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis.The immunogenicity of PEDV S-A and PEDV S-B subunit vaccines were evaluated in mice.The results showed that PEDV-S-B vaccine could not only induce specific humoral and Th1 type-dominant cellular immune responses,but also stimulate PEDV-specific mucosal immune responses in mice.PEDV-S-B subunit vaccine is a novel candidate mucosal vaccine against PEDV infection.展开更多
This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive soluti...This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.展开更多
受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、...受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。展开更多
Objective To characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals. Methods HIV-1-specific CTL responses were analyzed by IFN-7 ELISPOT assay us...Objective To characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals. Methods HIV-1-specific CTL responses were analyzed by IFN-7 ELISPOT assay using overlapping peptides spanning the consensus sequences of HIV-1 clade C Tat and Rev proteins. Statistical analysis and graphical presentation were performed using SIGMAPLOT 10.0 and SIGMASTAT 3.5. For samples with a positive response, the magnitude of CTL responses was compared between HIV-1 C proteins by Wilcoxon rank sum test, and the significance threshold was P〈0.05. Results Tat and Rev were frequently recognized, with 23% and 52% of the tested individuals having detectable responses to these proteins, respectively. Several immunodominant regions were detected in Rev. No significant correlation was observed between the magnitude and breadth of CTL responses to regulatory proteins and the control of virus replication in this study. Conclusion Tat and Rev can serve as targets for HIV-l-specific CTL, and several immunodominant regions are detectable in Rev. Further characterization of epitopes and their role in virus control may shed light on pathogenesis of HIV- 1 natural infection and also be useful for the design and testing of candidate vaccines.展开更多
Equine herpesvirus-1 (EHV-1) remains one of the most common viral pathogens affecting horses worldwide presenting as a persistent infection which can establish latency in nerve ganglia (trigeminal ganglion), lymphoid ...Equine herpesvirus-1 (EHV-1) remains one of the most common viral pathogens affecting horses worldwide presenting as a persistent infection which can establish latency in nerve ganglia (trigeminal ganglion), lymphoid tissues of the respiratory tract and peripheral blood lymphocytes. EHV-1 infection induces both humoral and cellular immune responses in horses. Virus neutralising antibody, particularly in the nasopharynx, is to kill free virus shed from infected epithelial cells. Hence this antibody has important functions in reducing virus shedding and spreading infection to cohorts. Cellular immune responses, particularly those carried out by cytotoxic T lymphocyte (CTL), have been shown to be effective in killing virus-infected cells in vitro. This review underlines the state of knowledge regarding immunity to EHV-1 and also its interaction with equine lymphocyte. Finally, the review also includes the importance of the viral immediate early (IE) protein in the pathogenesis of EHV-1. This information can be used as the basis for future research.展开更多
Nowadays,immunotherapy is widely used to treat different cancer types as it boosts the body's natural defenses against the malignancy,with lower risk of adverse events compared to the traditional treatments.The im...Nowadays,immunotherapy is widely used to treat different cancer types as it boosts the body's natural defenses against the malignancy,with lower risk of adverse events compared to the traditional treatments.The immune system is able to control cancer growth but,unfortunately,many cancers take advantage of immune checkpoints pathways for the immune evasion.An intricate network of factors including tumor,host and environmental variables influence the individual response to immune checkpoints’inhibitors.Between them,the gut microbiota(GM)has recently gained increasing attention because of its emerging role as a modulator of the immune response.Several studies analyzed the diversities between immunotherapy-sensitive and immunotherapy-resistant cohorts,evidencing that particular GM profiles were closely associated to treatment effect.In addition,other data documented that interventional GM modulation could effectively enhance efficacy and relieve resistance during immunotherapy treatment.Diet represents one of the major GM determinants,and ongoing studies are examining the role of the food-gut axis in immunotherapy treatment.Here,we review recent studies that described how variations of the GM affects patient’s responsivity to anti-cancer immunotherapy and how diet-related factors impact on the GM modulation in cancer,outlining potential future clinical directions of these recent findings.展开更多
High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-infl...High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.展开更多
基金supported by grants from the Brazilian Agencies:Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES-Financial code 001)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico(FUNCAP).
文摘Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.
基金This work was supported by the China National Basic Research Program(2016YFA0100203)National Natural Science Foundation of China(31572399Detail,32072806,32072815,32002246)+3 种基金State Key Lab of Reproductive Regulation&Breeding of Grassland Livestock(SKL-OT-201801)Science and Technology Major Project of Inner Mongolia Autonomous Region of China(ZDZX2018065)and Shaanxi Province Science and Technology Innovation Team(2019TD-036)The authors thank Dr.John Clotaire Daguia Zambe for helpful comments about this paper,Jia Fang for the PGL3-NF-κB luciferase reporter plasmid,and Dong-Xue Che for bioinformatics analysis.
文摘Double sex and mab-3-related transcription factor 1(Dmrt1),which is expressed in goat male germline stem cells(mGSCs)and Sertoli cells,is one of the most conserved transcription factors involved in sex determination.In this study,we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs.Dmrt1 recruited promyelocytic leukemia zinc finger(Plzf),also known as zinc finger and BTB domain-containing protein 16(Zbtb16),to repress the Toll-like receptor 4(TLR4)-dependent inflammatory signaling pathway and nuclear factor(NF)-κB.Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells,while the expression of proinflammatory factors were significantly enhanced.We also demonstrated that Dmrt1 stimulated proliferation of mGSCs,but repressed apoptosis caused by the immune response.Thus,Dmrt1 is sufficient to reduce inflammation in the testes,thereby establishing the stability of spermatogenesis and the testicular microenvironment.
文摘Foot-and-mouth disease virus (FMDV) is highly contagious and responsible for huge outbreaks among cloven hoofed animals. The aim of the present study is to evaluate a plasmid DNA immunization system that expresses the FMDV/OflRN/2007 VP1 gene and compare it with the conventional inactivated vaccine in an animal model. The VP1 gene was sub-cloned into the unique Kpn I and BamH I cloning sites of the peDNA3.1+ and pEGFP-N1 vectors to construct the VPI gene cassettes. The transfected BHKT7 cells with sub-cloned pEGFP-N1-VP1 vector expressed GFP-VP1 fusion protein and displayed more green fluorescence spots than the transfected BHKT7 cells with pEGFP-N1 vector, which solely expressed the GFP protein. Six mice groups were respectively immunized by the sub-cloned pcDNA3.1+-VP1 gene cassette as the DNA vaccine, DNA vaccine and PCMV-SPORT-GMCSF vector (as molecular adjuvant) together, conventional vaccine, PBS (as negative control), pcDNA3.1+ vector (as control group) and PCMV-SPORT vector that contained the GMCSF gene (as control group). Significant neutralizing antibody responses were induced in the mice which were immunized using plasmid vectors expressing the VP1 and GMCSF genes together, the DNA vaccine alone and the conventional inactivated vaccine (P〈0.05). Co-administration of DNA vaccine and GMCSF gene improved neutralizing antibody response in comparison with administration of the DNA vaccine alone, but this response was the most for the conventional vaccine group. However, induction of humeral immunity response in the conventional vaccine group was more protective than for the DNA vaccine, but T-cell proliferation and IFN-? concentration were the most in DNA vaccine with the GMCSF gene. Therefore the group that was vaccinated by DNA vaccine with the GMCSF gene, showed protective neutralizing antibody response and the most Thl cellular immunity.
文摘Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the parasite can exert several immune suppressive mechanisms that facilitate escaping the immune responses.One of these mechanisms is the up-regulation of programmed death-1/programmed death ligand-1 pathway which causes T cells to undergo exhaustion.Autophagy is strongly linked to the immune response,with some research indicating that activating autophagy reduces the immune response to some intracellular pathogens,while others indicate that activating autophagy limits the growth of intracellular pathogens.Leishmania was found to subvert the host defense mechanisms for its own persistence,such as Leishmania-induced autophagy modulation.Leishmania was reported to activate autophagy in different studies,thus getting a dual benefit by evading the immune system and simultaneously utilizing the autophagy byproducts as nutrients.In this review,we introduced different immune evasion/suppressive mechanisms used by Leishmania,and different immunotherapies which were developed accordingly.We focused on the programmed death-1/programmed death ligand-1 pathway as well as autophagy with the potential interplay of both mechanisms.
基金Supported by A Grant-in-Aid for Scientific Research from the Ministry of Education,Science,Sports,and Culture(MEXT)of JapanA Grant-in-Aid for AIDS Research from the Ministry of Health,Labor,and Welfare of Japan+1 种基金The Scholarship for the International Priority Graduate Programs,to Hasan Z and Kamori DAdvanced Graduate Courses for International Students(Doctoral Course),MEXT,Japan,to Hasan Z and Kamori D
文摘Viral protein U (Vpu) is an accessory protein associated with two main functions important in human immu-nodeficiency virus type 1 (HIV-1) replication and dis-semination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and en-hancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen inter-action is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo . In order to compre-hensively understand Vpu variability, it is important to integrate at the population level the genetic association approaches to identify specifc amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo . This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune re-sponses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu func-tional implication in HIV-1 pathogenesis.
基金the National Natural Science Foundation of China (No. 30000070)
文摘The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6–8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P〈0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P〈0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
文摘Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.
文摘Objective: To study the correlation of IRAK1 and TRAF6 expression with inflammatory response and immune response in oral lichen planus lesions. Methods: Patients who were diagnosed with oral lichen planus in Ziyang First People's Hospital between June 2014 and February 2017 were selected as the OLP group of the study, and the oral lichen planus lesions were collected;42 patients who accepted surgery for oral trauma or maxillofacial plastic surgery were selected as the control group of the study, and the normal oral mucosa tissue was collected. The expression of IRAK1, TRAF6 and TLR4 signaling pathway molecules, Th1/Th2/Treg/Th17 transcription factors and cytokines in tissue samples were detected. Results:IRAK1, TRAF6, TLR4, MyD88 and NF-kB mRNA expression and protein expression in oral lichen planus lesions of OLP patients were significantly lower than those of control group, T-bet and IFN-γ levels were significantly lower than those of control group, and GATA3, FOXP3, RORγt, IL-4, IL-10 and IL-17 levels were significantly higher than those of control group;IRAK1 and TRAF6 expression in oral mucosa tissue were positively correlated with TLR4, MyD88 and NF-kB expression as well as T-bet and IFN-γ levels, and were negatively correlated with GATA3, FOXP3, RORγt, IL-4, IL-10 and IL-17 levels. Conclusion: IRAK1 and TRAF6 expression in oral lichen planus lesions can inhibit the TLR4 inflammatory response pathway and lead to Th1/Th2 /Treg/Th17 immune response disorder.
基金the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)and 81601084(to YC)+3 种基金the National Key Research and Development Program of China,No.2017YFA0104304(to BW)the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science of China,No.201803024(to TYG)Innovation Platform,No.ZDX16005(to BW)。
文摘Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.
文摘Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with asthma.We assessed asthma by Asthma Control Test,the lung function by spirometry before and after the bronchodilator test,followed by collecting induced sputum.The next day,we collected exhaled breath condensate(EBC)and conducted a 3-minute isocapnic hyperventilation with cold air(IHCA),followed by collecting spontaneously produced sputum.Results:Group 1 included 20 patients with cold airway hyperresponsiveness(CAHR),and group 2 included 22 patients without CAHR.In both groups,a high level of neutrophils in bronchial secretion was observed before and after IHCA.In response to IHCA,the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γafter IHCA had an inverse relationship(r=-0.60;P=0.017).The baseline IFN-γin EBC before and after IHCA was lower in group 1.Airway response to cold exposure directly correlated with IFN-γlevels after IHCA(Rs=0.42;P=0.014).Conclusion:In asthma patients with CAHR,there is a relationship between the persistence of mixed inflammation and the level of IFN-γin the bronchi.IFN-γin response to IHCA is decreased with increased cytokine utilization during cold bronchospasm,which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells(Th)1 immune response.
基金This research was funded by the National Natural Science Foundation of China(31900746 and 31802170)Postdoctoral Science Foundation(2019M660182).
文摘Porcine epidemic diarrhea(PED)caused by the porcine epidemic diarrhea virus(PEDV),is a severe infectious and devastating swine disease that leads to serious economic losses in the swine industry worldwide.An increased number of PED cases caused by variant PEDV have been reported in many countries since 2010.S protein is the main immunogenic protein containing some B-cell epitopes that can induce neutralizing antibodies of PEDV.In this study,the construction,expression and purification of Pseudomonas aeruginosa exotoxin A(PE)without domain Ⅲ(PE△Ⅲ)as a vector was performed for the delivery of PEDV S-A or S-B.PE(△Ⅲ)PEDV S-A and PE(△Ⅲ)PEDV S-B recombinant proteins were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis.The immunogenicity of PEDV S-A and PEDV S-B subunit vaccines were evaluated in mice.The results showed that PEDV-S-B vaccine could not only induce specific humoral and Th1 type-dominant cellular immune responses,but also stimulate PEDV-specific mucosal immune responses in mice.PEDV-S-B subunit vaccine is a novel candidate mucosal vaccine against PEDV infection.
文摘This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.
文摘受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。
基金Ministry of Science and Technology of China (No. 2004BA719A01, 2006 CB 504207)
文摘Objective To characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals. Methods HIV-1-specific CTL responses were analyzed by IFN-7 ELISPOT assay using overlapping peptides spanning the consensus sequences of HIV-1 clade C Tat and Rev proteins. Statistical analysis and graphical presentation were performed using SIGMAPLOT 10.0 and SIGMASTAT 3.5. For samples with a positive response, the magnitude of CTL responses was compared between HIV-1 C proteins by Wilcoxon rank sum test, and the significance threshold was P〈0.05. Results Tat and Rev were frequently recognized, with 23% and 52% of the tested individuals having detectable responses to these proteins, respectively. Several immunodominant regions were detected in Rev. No significant correlation was observed between the magnitude and breadth of CTL responses to regulatory proteins and the control of virus replication in this study. Conclusion Tat and Rev can serve as targets for HIV-l-specific CTL, and several immunodominant regions are detectable in Rev. Further characterization of epitopes and their role in virus control may shed light on pathogenesis of HIV- 1 natural infection and also be useful for the design and testing of candidate vaccines.
文摘Equine herpesvirus-1 (EHV-1) remains one of the most common viral pathogens affecting horses worldwide presenting as a persistent infection which can establish latency in nerve ganglia (trigeminal ganglion), lymphoid tissues of the respiratory tract and peripheral blood lymphocytes. EHV-1 infection induces both humoral and cellular immune responses in horses. Virus neutralising antibody, particularly in the nasopharynx, is to kill free virus shed from infected epithelial cells. Hence this antibody has important functions in reducing virus shedding and spreading infection to cohorts. Cellular immune responses, particularly those carried out by cytotoxic T lymphocyte (CTL), have been shown to be effective in killing virus-infected cells in vitro. This review underlines the state of knowledge regarding immunity to EHV-1 and also its interaction with equine lymphocyte. Finally, the review also includes the importance of the viral immediate early (IE) protein in the pathogenesis of EHV-1. This information can be used as the basis for future research.
基金Supported by the Italian Ministry of University and Research,the Foundation“Ente Cassa di Risparmio di Firenze”FCR 2017Italian Ministry of Health(Ricerca Finalizzata 2016),No.GR-2016-02361162.
文摘Nowadays,immunotherapy is widely used to treat different cancer types as it boosts the body's natural defenses against the malignancy,with lower risk of adverse events compared to the traditional treatments.The immune system is able to control cancer growth but,unfortunately,many cancers take advantage of immune checkpoints pathways for the immune evasion.An intricate network of factors including tumor,host and environmental variables influence the individual response to immune checkpoints’inhibitors.Between them,the gut microbiota(GM)has recently gained increasing attention because of its emerging role as a modulator of the immune response.Several studies analyzed the diversities between immunotherapy-sensitive and immunotherapy-resistant cohorts,evidencing that particular GM profiles were closely associated to treatment effect.In addition,other data documented that interventional GM modulation could effectively enhance efficacy and relieve resistance during immunotherapy treatment.Diet represents one of the major GM determinants,and ongoing studies are examining the role of the food-gut axis in immunotherapy treatment.Here,we review recent studies that described how variations of the GM affects patient’s responsivity to anti-cancer immunotherapy and how diet-related factors impact on the GM modulation in cancer,outlining potential future clinical directions of these recent findings.
基金supported,in part,by grants from the National Natural Science Foundation(81130035,30971192,81071545,81272090,81121004)the National Basic Research Program of China(2012CB518102)
文摘High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.