气候变化领域集成服务门户(CCPortal): The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms

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DOI	10.1073/pnas.1911646117
	The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms
	Lienard J.; Nobs E.; Lovins V.; Movert E.; Valfridsson C.; Carlsson F.
发表日期	2020
ISSN	0027-8424
起始页码	1160
结束页码	1166
卷号	117 期号:2
英文摘要	Following mycobacterial entry into macrophages the ESX-1 type VII secretion system promotes phagosomal permeabilization and type I IFN production, key features of tuberculosis pathogenesis. The current model states that the secreted substrate ESAT-6 is required for membrane permeabilization and that a subsequent passive leakage of extracellular bacterial DNA into the host cell cytosol is sensed by the cyclic GMP-AMP synthase (cGAS) and stimulator of IFN genes (STING) pathway to induce type I IFN production. We employed a collection of Mycobacterium marinum ESX-1 transposon mutants in a macrophage infection model and show that permeabilization of the phagosomal membrane does not require ESAT-6 secretion. Moreover, loss of membrane integrity is insufficient to induce type I IFN production. Instead, type I IFN production requires intact ESX-1 function and correlates with release of mitochondrial and nuclear host DNA into the cytosol, indicating that ESX-1 affects host membrane integrity and DNA release via genetically separable mechanisms. These results suggest a revised model for major aspects of ESX-1-mediated host interactions and put focus on elucidating the mechanisms by which ESX-1 permeabilizes host membranes and induces the type I IFN response, questions of importance for our basic understanding of mycobacterial pathogenesis and innate immune sensing. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	ESAT-6 secretion; Membrane permeabilization; Mitochondrion; Mycobacterial pathogenesis; Type I interferon
语种	英语
scopus关键词	chaperonin 60; early secretory antigenic target 6; interferon; bacterial antigen; bacterial protein; ESAT-6 protein, Mycobacterium tuberculosis; interferon; Article; cell permeabilization; controlled study; cytokine production; cytosol; cytosolic fraction; host interaction; immunofluorescence microscopy; mycobacteriosis; Mycobacterium marinum; nonhuman; pathogenesis; phagosome; phenotype; priority journal; protein secretion; transposon; type VII secretion system; Western blotting; wild type; atypical mycobacteriosis; cell membrane permeability; genetics; host pathogen interaction; immunology; macrophage; metabolism; microbiology; mitochondrion; Mycobacterium marinum; pathogenicity; physiology; tuberculosis; type VII secretion system; Antigens, Bacterial; Bacterial Proteins; Cell Membrane Permeability; Host-Pathogen Interactions; Interferon Type I; Macrophages; Mitochondria; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Phagosomes; Tuberculosis; Type VII Secretion Systems
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160322
作者单位	Lienard, J., Department of Biology, Section for Molecular Cell Biology, Lund University, Lund, 223 62, Sweden; Nobs, E., Department of Biology, Section for Molecular Cell Biology, Lund University, Lund, 223 62, Sweden; Lovins, V., Department of Biology, Section for Molecular Cell Biology, Lund University, Lund, 223 62, Sweden, Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Movert, E., Department of Experimental Medical Science, Section for Immunology, Lund University, Lund, 221 84, Sweden; Valfridsson, C., Department of Experimental Medical Science, Section for Immunology, Lund University, Lund, 221 84, Sweden; Carlsson, F., Department of Biology, Section for Molecular Cell Biology, Lund University, Lund, 223 62, Sweden
推荐引用方式 GB/T 7714	Lienard J.,Nobs E.,Lovins V.,et al. The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms[J],2020,117(2).
APA	Lienard J.,Nobs E.,Lovins V.,Movert E.,Valfridsson C.,&Carlsson F..(2020).The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms.Proceedings of the National Academy of Sciences of the United States of America,117(2).
MLA	Lienard J.,et al."The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms".Proceedings of the National Academy of Sciences of the United States of America 117.2(2020).