Macrophages exploit the mannose receptor and JAK-STAT1- MHC-Ⅱ pathway to drive antigen presentation and the antimycobacterial immune response after BCG vaccination  

作　　者：Ying Zhang Dandan Xu Qi Nie Jing Wang Dan Fang Yan Xie Huang Xiong Qin Pan Xiao-Lian Zhang 

机构地区：[1]Department of Immunology,Wuhan University Taikang Medical School(School of Basic Medical Sciences),Department of Allergy of Zhongnan Hospital and Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University,Wuhan 430071,China [2]State Key Laboratory of Virology,Medical Research Institute and Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan 430071,China [3]Department of Blood Transfusion,the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University,Xuzhou First People’s Hospital,Xuzhou 221116,China [4]Wuhan Jinyintan Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430023,China [5]Department of Anatomy,Wuhan University Taikang Medical School(School of Basic Medical Sciences)and Hubei Province Key Laboratory of Allergy and Immunology,Wuhan 430071,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第8期1130-1144,共15页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Key R&D Program of China(Nos.2022YFA1303500 and 2018YFA0507603);the National Natural Science Foundation of China(Nos.82230078,22077097,91740120,21721005,82272978 and 21572173);the Fundamental Research Funds for the Central Universities.

摘　　要：Tuberculosis(TB),caused by Mycobacterium tuberculosis(M.tb),remains one of the leading causes of fatal infectious diseases worldwide.The only licensed vaccine,Mycobacterium bovis Bacillus Calmette-Guérin(BCG),has variable efficacy against TB in adults.Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine.It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination.Macrophage mannose receptor(MR)is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells,but the roles of macrophageMRin the BCG-induced immune response against M.tb are not yet clear.Here,we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice.Mechanistically,macrophage MR triggers JAKSTAT1 signaling,which promotes antigen presentation via upregulated MHC-Ⅱ and induces IL-12 production by macrophages,contributing to CD4^(+)T cell activation and IFN-γ production.MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M.tb H37Ra challenge in mice.Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.

关 键 词：BCG vaccine mannose receptor MACROPHAGE antigen presentation 

分 类 号：R186[医药卫生—流行病学] R392[医药卫生—公共卫生与预防医学]