A human apolipoprotein L with detergent-like activity kills intracellular pathogens
| Autor: | Erdem Karatekin, Shiwei Zhu, Thanh Ngoc Nguyen, Michael Lazarou, Clinton J. Bradfield, John D. MacMicking, Kallol Gupta, Anushka Halder, Ryan G. Gaudet, Shuai Huang, Bae Hoon Kim, Agnieszka Maminska, Dijin Xu |
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| Rok vydání: | 2021 |
| Předmět: |
Salmonella typhimurium
Cell Membrane Permeability Extracellular transport Lipoproteins Detergents Lysin Interferon-gamma 03 medical and health sciences Bacteriolysis Cytosol 0302 clinical medicine Immune system Protein Domains GTP-Binding Proteins Interferon Apolipoproteins L Gram-Negative Bacteria Extracellular medicine Humans Cells Cultured 030304 developmental biology Gene Editing 0303 health sciences Microbial Viability Multidisciplinary Chemistry Intracellular parasite Cell Membrane O Antigens Immunity Innate Cell biology Bacterial Outer Membrane Solubility CRISPR-Cas Systems 030217 neurology & neurosurgery Intracellular medicine.drug Lipoprotein |
| Zdroj: | Science. 373 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Cleansing the cytosol Most human cells, not just those belonging to the immune system, mount protective responses to infection when activated by the immune cytokine interferon-gamma (IFN-γ). How IFN-γ confers this function in nonimmune cells and tissues is poorly understood. Gaudet et al. used genome-scale CRISPR/Cas9 gene editing to identify apolipoprotein L-3 (APOL3) as an IFN-γ–induced bactericidal protein that protects human epithelium, endothelium, and fibroblasts against infection (see the Perspective by Nathan). APOL3 directly targets bacteria in the host cell cytosol and kills them by dissolving their anionic membranes into lipoprotein complexes. This work reveals a detergent-like mechanism enlisted during human cell-autonomous immunity to combat intracellular pathogens. Science , abf8113, this issue p. eabf8113 ; see also abj5637, p. 276 |
| Databáze: | OpenAIRE |
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