globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1911646117
论文题名:
The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms
作者: Lienard J.; Nobs E.; Lovins V.; Movert E.; Valfridsson C.; Carlsson F.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2020
卷: 117, 期:2
起始页码: 1160
结束页码: 1166
语种: 英语
英文关键词: ESAT-6 secretion ; Membrane permeabilization ; Mitochondrion ; Mycobacterial pathogenesis ; Type I interferon
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
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.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163502
Appears in Collections:气候变化与战略

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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

Recommended Citation:
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]. Proceedings of the National Academy of Sciences of the United States of America,2020-01-01,117(2)
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