Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection
| Autor: | Sindre Ullmann, Markus Haug, Trine Aakvik Strand, Signe Elisabeth Åsberg, Michael Niederweis, Kai Sandvold Beckwith, Harald Stenmark, Anne Marstad, Ragnhild Sofie Ragnhildstveit Sætra, Marianne Sandvold Beckwith, Haelin Kim, Trude Helen Flo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell death
0301 basic medicine Inflammasomes THP-1 Cells Science Phagocytosis Green Fluorescent Proteins General Physics and Astronomy Article General Biochemistry Genetics and Molecular Biology Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Bacterial Proteins Phagosomes NLR Family Pyrin Domain-Containing 3 Protein Pyroptosis Tuberculosis Humans Secretion lcsh:Science Innate immunity Antigens Bacterial Multidisciplinary biology Chemistry Immune cell death Cell Membrane Plasma membrane repair General Chemistry Hydrogen-Ion Concentration biology.organism_classification Cathepsins Mitochondria 3. Good health Cell biology Cytosol 030104 developmental biology Imaging the immune system lcsh:Q Efflux 030217 neurology & neurosurgery Bacteria |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-16143-6 |
| Popis: | Mycobacterium tuberculosis is a global health problem in part as a result of extensive cytotoxicity caused by the infection. Here, we show how M. tuberculosis causes caspase-1/NLRP3/gasdermin D-mediated pyroptosis of human monocytes and macrophages. A type VII secretion system (ESX-1) mediated, contact-induced plasma membrane damage response occurs during phagocytosis of bacteria. Alternatively, this can occur from the cytosolic side of the plasma membrane after phagosomal rupture in infected macrophages. This damage causes K+ efflux and activation of NLRP3-dependent IL-1β release and pyroptosis, facilitating the spread of bacteria to neighbouring cells. A dynamic interplay of pyroptosis with ESCRT-mediated plasma membrane repair also occurs. This dual plasma membrane damage seems to be a common mechanism for NLRP3 activators that function through lysosomal damage. Inflammasome activation is a response to bacterial infection but can cause damage and spread infection. Here, the authors use live single-cell imaging to show two mechanisms by which M. tuberculosis causes damage to human macrophage cell plasma membranes, resulting in activation of the NLRP3 inflammasome, pyroptosis and release of infectious particles. |
| Databáze: | OpenAIRE |
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