| Autor: |
Chanchal Sur Chowdhury, Rachel L. Kinsella, E. Michael Nehls, Sumanta K. Naik, Daniel S. Lane, Priyanka Talukdar, Sthefany M. Chavez, Asya Smirnov, Wandy Beatty, Darren Kreamalmeyer, Joshua T. Mattila, Christina L. Stallings |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.11.29.518376 |
| Popis: |
SUMMARYNeutrophils are the most abundant cell type in airways of tuberculosis patients. Recent investigations reported induction of neutrophil extracellular traps (NETs) duringMycobacterium tuberculosis(Mtb) infection, however, the molecular regulation and impact of NETosis onMtbpathogenesis is unknown. We find that in response toMtbinfection in neutrophils, PAD4 citrullinates histones to decondense chromatin that gets packaged into vesicles for release as NETs in a manner that can maintain neutrophil viability and promoteMtbreplication. Type I interferon, which has been associated with NETosis in numerous contexts but without a known mechanism, promotes formation of chromatin-containing vesicles and NET release. Analysis of nonhuman primate granulomas supports a model where neutrophils are exposed to type I interferon from macrophages as they migrate into the granuloma, where they release NETs that contribute to necrosis and caseation. Our data reveals NETosis as a promising target to inhibitMtbreplication and granuloma caseation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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