Hif-1α-Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish.

Autor:	Ogryzko NV; The Bateson Centre, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.; Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom., Lewis A; The Bateson Centre, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Western Bank, Sheffield S10 2RX, United Kingdom; and., Wilson HL; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Western Bank, Sheffield S10 2RX, United Kingdom; and., Meijer AH; Institute of Biology, Leiden University, 2333 CC Leiden, the Netherlands., Renshaw SA; The Bateson Centre, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Western Bank, Sheffield S10 2RX, United Kingdom; and., Elks PM; The Bateson Centre, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom; p.elks@sheffield.ac.uk.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Western Bank, Sheffield S10 2RX, United Kingdom; and.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jan 15; Vol. 202 (2), pp. 494-502. Date of Electronic Publication: 2018 Dec 14.
DOI:	10.4049/jimmunol.1801139
Abstrakt:	Drug-resistant mycobacteria are a rising problem worldwide. There is an urgent need to understand the immune response to tuberculosis to identify host targets that, if targeted therapeutically, could be used to tackle these currently untreatable infections. In this study we use an Il-1β fluorescent transgenic line to show that there is an early innate immune proinflammatory response to well-established zebrafish models of inflammation and Mycobacterium marinum infection. We demonstrate that host-derived hypoxia signaling, mediated by the Hif-1α transcription factor, can prime macrophages with increased levels of Il-1β in the absence of infection, upregulating neutrophil antimicrobial NO production, leading to greater protection against infection. Our data link Hif-1α to proinflammatory macrophage Il-1β transcription in vivo during early mycobacterial infection and importantly highlight a host protective mechanism, via antimicrobial NO, that decreases disease outcomes and that could be targeted therapeutically to stimulate the innate immune response to better deal with infections. (Copyright © 2019 The Authors.)
Databáze:	MEDLINE
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