The worldwide dissemination of drug-resistant tuberculosis(TB)presents significant obstacles to conventional antiTB treatment and prevention methods based on bactericidal antimicrobial drugs,greatly impeding advanceme...The worldwide dissemination of drug-resistant tuberculosis(TB)presents significant obstacles to conventional antiTB treatment and prevention methods based on bactericidal antimicrobial drugs,greatly impeding advancements in combating this most lethal disease.With growing insights into the immunopathogenesis of TB,we are increasingly recognizing the potential of immunotherapeutic strategies aimed at targeting the host.After invading the host,Mycobacterium tuberculosis(M.tuberculosis)induces host cell exhaustion through its own molecules,such as early secretory antigen target-6(ESAT-6)and di-O-acyl-trehalose,manifested as suppressed proliferative capacity,cytokine production,and cytotoxicity,thereby triggering the onset of TB.In response to this pathogenic mechanism,immunotherapeutic strategies,including cell therapy and immune checkpoint inhibitors,have been developed to promote cytokine production,activate immune cells to exhibit anti-TB activities such as autophagy,and restore immune homeostasis,including the balance between T helper 1(Th1)and Th2 responses.These approaches have shown promise in restoring host immunity and demonstrating therapeutic effects against TB.However,a comprehensive evaluation of factors such as drug safety,optimal treatment duration,and others,is essential before these strategies can be integrated into routine clinical TB management.The advancement of immunotherapy has the potential to revolutionize current TB management and provide further benefits to patients.This review aims to comprehensively explore the advancements in diverse TB immunotherapeutic strategies,including efficacy,safety,and administration methods,and to explore the challenges and prospects of TB immunotherapy.展开更多
T lymphopenia,occurring in the early phase of sepsis in response to systemic inflammation,is commonly associated with morbidity and mortality of septic infections.We have previously shown that a sufficient number of T...T lymphopenia,occurring in the early phase of sepsis in response to systemic inflammation,is commonly associated with morbidity and mortality of septic infections.We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors(TLRs)mediated hyperinflammation.However,the underlying mechanisms remains unsolved.Herein,we unveil that CD4^(+)T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling.展开更多
基金supported by the National Natural Science Foundation of China(82302624,82102968,and 82272416)the Natural Science Foundation of Sichuan Province(2024NSFSC1548)the Post-Doctoral Research Project of West China Hospital Sichuan University(2023HXBH069)。
文摘The worldwide dissemination of drug-resistant tuberculosis(TB)presents significant obstacles to conventional antiTB treatment and prevention methods based on bactericidal antimicrobial drugs,greatly impeding advancements in combating this most lethal disease.With growing insights into the immunopathogenesis of TB,we are increasingly recognizing the potential of immunotherapeutic strategies aimed at targeting the host.After invading the host,Mycobacterium tuberculosis(M.tuberculosis)induces host cell exhaustion through its own molecules,such as early secretory antigen target-6(ESAT-6)and di-O-acyl-trehalose,manifested as suppressed proliferative capacity,cytokine production,and cytotoxicity,thereby triggering the onset of TB.In response to this pathogenic mechanism,immunotherapeutic strategies,including cell therapy and immune checkpoint inhibitors,have been developed to promote cytokine production,activate immune cells to exhibit anti-TB activities such as autophagy,and restore immune homeostasis,including the balance between T helper 1(Th1)and Th2 responses.These approaches have shown promise in restoring host immunity and demonstrating therapeutic effects against TB.However,a comprehensive evaluation of factors such as drug safety,optimal treatment duration,and others,is essential before these strategies can be integrated into routine clinical TB management.The advancement of immunotherapy has the potential to revolutionize current TB management and provide further benefits to patients.This review aims to comprehensively explore the advancements in diverse TB immunotherapeutic strategies,including efficacy,safety,and administration methods,and to explore the challenges and prospects of TB immunotherapy.
基金All authors are grateful to Dr.Xue-tao Cao(The Second Military Medical University,Shanghai)for providing MHC II−/−mice,and Dr.Geoege F.Gao(Institute of Microbiology,CAS)for producing recombinant sCD4 at certain stage of this study.Drs.Hai-rong Chen(Institute of Biophysics,CAS)and Ya-ming Jiu(Institut Pasteur of Shanghai)also provided key technical assistance to the study.We also thank Drs.Yang-xin Fu(Tsinghua University)and Lan-juan Li(Zhejiang University)for their inspiring advice.The work was supported in part by grants from Chinese Academy of Sciences(XDB29030301,153831KYSB20160038,QYZDJ-SSW-SMC026)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)and NSFC(81530067)to H.T,Bill&Melinda Gates Foundation,Shenzhen Municipal Science and Technology Innovation Committee(202002073000002)and NSFC(91442127)to Z.Z+2 种基金National Science and Technology Major Projects of China to H.T.(2020YFC0845900)and S.L.(2018ZX10101004002004)Shanghai Municipal Natural Sciences Foundation to S.L.(19ZR1463100)and H.P.(20SWAQX23-004-002)S.L is a fellow of Youth Association of Innovation Promotion,CAS.
文摘T lymphopenia,occurring in the early phase of sepsis in response to systemic inflammation,is commonly associated with morbidity and mortality of septic infections.We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors(TLRs)mediated hyperinflammation.However,the underlying mechanisms remains unsolved.Herein,we unveil that CD4^(+)T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling.
