抗原
生物
抗原呈递
T细胞
效应器
ESCRT公司
抗原提呈细胞
结核分枝杆菌
免疫系统
细胞生物学
主要组织相容性复合体
内体
微生物学
免疫学
肺结核
医学
病理
细胞内
作者
Cynthia Portal‐Celhay,JoAnn M. Tufariello,Smita Srivastava,Aleena Zahra,Thaís Klevorn,Patricia S. Grace,Alka Mehra,Heidi S. Park,J. Ernst,William R. Jacobs,Jennifer A. Philips
出处
期刊:Nature microbiology
日期:2016-12-05
卷期号:2 (2)
被引量:86
标识
DOI:10.1038/nmicrobiol.2016.232
摘要
Mycobacterium tuberculosis (Mtb) establishes a persistent infection, despite inducing antigen-specific T-cell responses. Although T cells arrive at the site of infection, they do not provide sterilizing immunity. The molecular basis of how Mtb impairs T-cell function is not clear. Mtb has been reported to block major histocompatibility complex class II (MHC-II) antigen presentation; however, no bacterial effector or host-cell target mediating this effect has been identified. We recently found that Mtb EsxH, which is secreted by the Esx-3 type VII secretion system, directly inhibits the endosomal sorting complex required for transport (ESCRT) machinery. Here, we showed that ESCRT is required for optimal antigen processing; correspondingly, overexpression and loss-of-function studies demonstrated that EsxH inhibited the ability of macrophages and dendritic cells to activate Mtb antigen-specific CD4+ T cells. Compared with the wild-type strain, the esxH-deficient strain induced fivefold more antigen-specific CD4+ T-cell proliferation in the mediastinal lymph nodes of mice. We also found that EsxH undermined the ability of effector CD4+ T cells to recognize infected macrophages and clear Mtb. These results provide a molecular explanation for how Mtb impairs the adaptive immune response.
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