SNX10 promotes phagosome maturation in macrophages and protects mice against Listeria monocytogenes infection.
SNX10 promotes phagosome maturation in macrophages and protects mice against Listeria monocytogenes infection.
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SNX10 促进巨噬细胞吞噬体成熟并保护小鼠免受单核细胞增生李斯特菌感染
DOI：
10.18632/oncotarget.19644
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发表时间：
2017-08-15
期刊：
影响因子：
--
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Lou J;Li X;Huang W;Liang J;Zheng M;Xu T;Lyu J;Li D;Xu Q;Jin X;Fu G;Wang D;Lu L
单核细胞增生李斯特菌（Listeria monocytogenes，L.单核细胞增多症），其是引起单核细胞增多症的兼性细胞内细菌病原体，被广泛用于研究哺乳动物对感染的免疫应答。经专职吞噬细胞吞噬后，L.单核细胞增多症最初包含在吞噬体中，吞噬体成熟为吞噬溶酶体，细菌在吞噬溶酶体中降解。虽然吞噬作用和随后的吞噬体成熟对于感染性微生物病原体的清除是必不可少的，但潜在的调节机制仍不清楚。SNX 10（Sorting nexin 10）具有SNX家族中最简单的结构，并且已被报道调节内体形态，这可能对巨噬细胞功能至关重要，包括病原体的吞噬和消化、炎症反应和抗原呈递。我们的结果表明，SNX 10表达上调L。巨噬细胞中的单核细胞增多症感染。还揭示了SNX 10通过将Mon 1-Ccz 1复合物募集到内体和吞噬体来促进吞噬体成熟。结果，SNX 10缺陷降低了巨噬细胞的杀菌能力，SNX 10缺陷小鼠对L.体内单核细胞增多症感染。因此，这项研究揭示了SNX 10在控制细菌感染中的重要作用。
Listeria monocytogenes (L. monocytogenes), which is a facultative intracellular bacterial pathogen that causes listeriosis, is widely used to study the mammalian immune response to infection. After phagocytosis by professional phagocytes, L. monocytogenes is initially contained within phagosomes, which mature into phagolysosomes, where the bacteria are degraded. Although phagocytosis and subsequent phagosome maturation is essential for the clearance of infectious microbial pathogens, the underlying regulatory mechanisms are still unclear. SNX10 (Sorting nexin 10) has the simplest structure of the SNX family and has been reported to regulate endosomal morphology, which might be crucial for macrophage function, including phagocytosis and digestion of pathogens, inflammatory response, and antigen presentation. Our results showed that SNX10 expression was upregulated following L. monocytogenes infection in macrophages. It was also revealed that SNX10 promoted phagosome maturation by recruiting the Mon1-Ccz1 complex to endosomes and phagosomes. As a result, SNX10 deficiency decreased the bacterial killing ability of macrophages, and SNX10-deficient mice showed increased susceptibility to L. monocytogenes infection in vivo. Thus, this study revealed an essential role of SNX10 in controlling bacterial infection.