Mycobacterium tuberculosis PPE18 protein inhibits MHC class II antigen presentation and B cell response in mice,European Journal of Immunology

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Mycobacterium tuberculosis PPE18 protein inhibits MHC class II antigen presentation and B cell response in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-10-20 , DOI: 10.1002/eji.201848071
Komal Dolasia _{1,

2} , Faiza Nazar ₁ , Sangita Mukhopadhyay ₁

Affiliation

PPE18 protein belongs to PE/PPE family of Mycobacterium tuberculosis. We reported earlier that PPE18 protein provides survival advantage to M. tuberculosis during infection. In the current study, we found that PPE18 inhibits MHC class II‐mediated antigen presentation by macrophages in a dose‐dependent manner without affecting the surface level of MHC class II or co‐stimulatory molecules. PPE18 does not affect antigen uptake or presentation of preprocessed peptide by macrophages. Antigen degradation was found to be inhibited by PPE18 protein due to perturbation in phagolysosomal acidification. PPE18‐mediated inhibition of MHC class II antigen presentation caused poorer activation of CD4 T cells. Mice infected with M. smegmatis expressing PPE18 exhibited reduced maturation and activation of B cells and had decreased Mycobacteria‐specific antibody titers. Thus M. tuberculosis probably utilizes PPE18 to inhibit MHC class II antigen presentation causing poorer activation of adaptive immune responses. This study may be useful in understanding host–pathogen interaction and open up directions of designing novel therapeutics targeting PPE18 to tackle this nefarious pathogen.

中文翻译：

结核分枝杆菌 PPE18 蛋白抑制小鼠 MHC II 类抗原呈递和 B 细胞反应

PPE18蛋白属于结核分枝杆菌的PE/PPE家族。我们之前报道过 PPE18 蛋白在感染期间为结核分枝杆菌提供了生存优势。在目前的研究中，我们发现 PPE18 以剂量依赖的方式抑制 MHC II 类介导的巨噬细胞抗原呈递，而不影响 MHC II 类或共刺激分子的表面水平。PPE18 不影响巨噬细胞对抗原摄取或预处理肽的呈递。由于吞噬溶酶体酸化的扰动，发现抗原降解被 PPE18 蛋白抑制。PPE18 介导的 MHC II 类抗原呈递抑制导致 CD4 T 细胞活化较差。感染耻垢分枝杆菌的小鼠表达 PPE18 表现出 B 细胞的成熟和活化减少，并且分枝杆菌特异性抗体滴度降低。因此，结核分枝杆菌可能利用 PPE18 抑制 MHC II 类抗原呈递，导致适应性免疫反应的激活较差。这项研究可能有助于理解宿主 - 病原体的相互作用，并开辟设计针对 PPE18 的新型疗法以应对这种邪恶病原体的方向。

更新日期：2020-10-20

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