线粒体对巨噬细胞抗病原体反应的调节
Mitochondrial Regulation of Macrophage Response Against Pathogens.
作者信息
Choudhuri Subhadip, Chowdhury Imran Hussain, Garg Nisha Jain
机构信息
Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, TX, United States.
Institute for Human Infections and Immunity, UTMB, Galveston, TX, United States.
出版信息
Front Immunol. 2021 Feb 17;11:622602. doi: 10.3389/fimmu.2020.622602. eCollection 2020.
Abstract
Innate immune cells play the first line of defense against pathogens. Phagocytosis or invasion by pathogens can affect mitochondrial metabolism in macrophages by diverse mechanisms and shape the macrophage response (proinflammatory . immunomodulatory) against pathogens. Besides β-nicotinamide adenine dinucleotide 2'-phosphate, reduced (NADPH) oxidase, mitochondrial electron transport chain complexes release superoxide for direct killing of the pathogen. Mitochondria that are injured are removed by mitophagy, and this process can be critical for regulating macrophage activation. For example, impaired mitophagy can result in cytosolic leakage of mitochondrial DNA (mtDNA) that can lead to activation of cGAS-STING signaling pathway of macrophage proinflammatory response. In this review, we will discuss how metabolism, mtDNA, mitophagy, and cGAS-STING pathway shape the macrophage response to infectious agents.
摘要
先天免疫细胞对病原体起着第一道防线的作用。病原体的吞噬作用或入侵可通过多种机制影响巨噬细胞中的线粒体代谢，并塑造巨噬细胞针对病原体的反应（促炎、免疫调节）。除了β-烟酰胺腺嘌呤二核苷酸2'-磷酸、还原型（NADPH）氧化酶外，线粒体电子传递链复合物还释放超氧化物以直接杀死病原体。受损的线粒体通过线粒体自噬被清除，这一过程对于调节巨噬细胞活化可能至关重要。例如，线粒体自噬受损可导致线粒体DNA（mtDNA）的胞质泄漏，从而导致巨噬细胞促炎反应的cGAS-STING信号通路激活。在本综述中，我们将讨论代谢、mtDNA、线粒体自噬和cGAS-STING通路如何塑造巨噬细胞对感染因子的反应。
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