Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
PLoS One. 2013 Dec 23;8(12):e86017. doi: 10.1371/journal.pone.0086017. eCollection 2013.
Mycobacterium tuberculosis is an intracellular pathogen that can survive within phagocytic cells by inhibiting phagolysosome biogenesis. However, host cells can control the intracellular M. tuberculosis burden by the induction of autophagy. The mechanism of autophagosome formation to M. tuberculosis has been well studied in macrophages, but remains unclear in dendritic cells. We therefore characterized autophagosome formation in response to M. tuberculosis infection in dendritic cells. Autophagy marker protein LC3, autophagy adaptor protein p62/SQSTM1 (p62) and ubiquitin co-localized to M. tuberculosis in dendritic cells. Mycobacterial autophagosomes fused with lysosomes during infection, and major histcompatibility complex class II molecules (MHC II) also localized to mycobacterial autophagosomes. The proteins p62 and Atg5 function in the initiation and progression of autophagosome formation to M. tuberculosis, respectively; p62 mediates ubiquitination of M. tuberculosis and Atg5 is involved in the trafficking of degradative vesicles and MHC II to mycobacterial autophagosomes. These results imply that the autophagosome formation to M. tuberculosis in dendritic cells promotes the antigen presentation of mycobacterial peptides to CD4(+) T lymphocytes via MHC II.
结核分枝杆菌是一种细胞内病原体，能够通过抑制吞噬体生物发生在吞噬细胞内存活。然而，宿主细胞可以通过诱导自噬来控制细胞内结核分枝杆菌的负担。自噬体形成到结核分枝杆菌的机制在巨噬细胞中已经得到很好的研究，但在树突状细胞中仍然不清楚。因此，我们在树突状细胞中描述了结核分枝杆菌感染时自噬体的形成。自噬标志物蛋白 LC3、自噬衔接蛋白 p62/SQSTM1（p62）和泛素与树突状细胞中的结核分枝杆菌共定位。在感染过程中，分枝杆菌自噬体与溶酶体融合，主要组织相容性复合物 II 类分子（MHC II）也定位于分枝杆菌自噬体。蛋白 p62 和 Atg5 分别在分枝杆菌自噬体形成的起始和进展中起作用；p62 介导结核分枝杆菌的泛素化，而 Atg5 参与降解囊泡和 MHC II 向分枝杆菌自噬体的运输。这些结果表明，树突状细胞中结核分枝杆菌的自噬体形成通过 MHC II 促进了分枝杆菌肽向 CD4(+)T 淋巴细胞的抗原呈递。
