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The Mycobacterium m...
The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms
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- Lienard, Julia (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Nobs, Esther (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Lovins, Victoria (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,University of Pennsylvania
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- Movert, Elin (författare)
- Lund University,Lunds universitet,Infektionsimmunologi,Forskargrupper vid Lunds universitet,Infectious Immunology,Lund University Research Groups
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- Valfridsson, Christine (författare)
- Lund University,Lunds universitet,Infektionsimmunologi,Forskargrupper vid Lunds universitet,Infectious Immunology,Lund University Research Groups
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- Carlsson, Fredric (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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(creator_code:org_t)
- 2019-12-26
- 2020
- Engelska 7 s.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 117:2, s. 1160-1166
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.pnas.org...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Nyckelord
- ESAT-6 secretion
- Membrane permeabilization
- Mitochondrion
- Mycobacterial pathogenesis
- Type I interferon
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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