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分选连接蛋白10(SNX10)促进巨噬细胞中吞噬体的成熟,并保护小鼠免受感染。

SNX10 promotes phagosome maturation in macrophages and protects mice against infection.

作者信息

Lou Jun, Li Xiawei, Huang Wei, Liang Jingjing, Zheng Mingzhu, Xu Ting, Lyu Jun, Li Dan, Xu Qin, Jin Xuexiao, Fu Guotong, Wang Di, Lu Linrong

机构信息

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.

Program in Molecular and Cellular Biology, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Oncotarget. 2017 Jul 27;8(33):53935-53947. doi: 10.18632/oncotarget.19644. eCollection 2017 Aug 15.

Abstract

(), 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, 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 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 infection . Thus, this study revealed an essential role of SNX10 in controlling bacterial infection.

摘要

( )是一种导致李斯特菌病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反应。在被专职吞噬细胞吞噬后, 最初被包裹在吞噬体中,吞噬体随后成熟为吞噬溶酶体,细菌在其中被降解。尽管吞噬作用和随后的吞噬体成熟对于清除感染性微生物病原体至关重要,但其潜在的调节机制仍不清楚。分选连接蛋白10(SNX10)具有SNX家族中最简单的结构,据报道可调节内体形态,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、炎症反应以及抗原呈递。我们的结果表明,巨噬细胞感染 后SNX10表达上调。还发现SNX10通过将Mon1-Ccz1复合物招募到内体和吞噬体来促进吞噬体成熟。结果,SNX10缺陷降低了巨噬细胞的细菌杀伤能力,SNX10缺陷小鼠对 感染的易感性增加。因此,本研究揭示了SNX10在控制细菌感染中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed71/5589552/faad894a7828/oncotarget-08-53935-g001.jpg

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