Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nat Microbiol. 2016 Aug 15;1(9):16133. doi: 10.1038/nmicrobiol.2016.133.
Suppression of major histocompatibility complex (MHC) class II antigen presentation is believed to be among the major mechanisms used by Mycobacterium tuberculosis to escape protective host immune responses. Through a genome-wide screen for the genetic loci of M. tuberculosis that inhibit MHC class II-restricted antigen presentation by mycobacteria-infected dendritic cells, we identified the PE_PGRS47 protein as one of the responsible factors. Targeted disruption of the PE_PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo, and a PE_PGRS47 mutant showed enhanced MHC class II-restricted antigen presentation during in vivo infection of mice. Analysis of the effects of deletion or over-expression of PE_PGRS47 implicated this protein in the inhibition of autophagy in infected host phagocytes. Our findings identify PE_PGRS47 as a functionally relevant, non-redundant bacterial factor in the modulation of innate and adaptive immunity by M. tuberculosis, suggesting strategies for improving antigen presentation and the generation of protective immunity during vaccination or infection.
抑制主要组织相容性复合体（MHC）II 类抗原呈递被认为是结核分枝杆菌逃避保护性宿主免疫反应的主要机制之一。通过对结核分枝杆菌抑制分枝杆菌感染树突状细胞 MHC Ⅱ类限制性抗原呈递的遗传基因座进行全基因组筛选，我们发现 PE_PGRS47 蛋白是负责因素之一。靶向敲除 PE_PGRS47（Rv2741）基因导致结核分枝杆菌在体外和体内生长减弱，PE_PGRS47 突变体在体内感染小鼠时表现出增强的 MHC Ⅱ类限制性抗原呈递。对 PE_PGRS47 缺失或过表达的影响分析表明，该蛋白参与了感染宿主吞噬细胞自噬的抑制。我们的研究结果表明，PE_PGRS47 是结核分枝杆菌调节先天和适应性免疫的一种功能相关的、非冗余的细菌因子，提示在接种或感染期间改善抗原呈递和产生保护性免疫的策略。
