Ogryzko, N.V. orcid.org/0000-0003-0199-5567, Lewis, A. orcid.org/0000-0002-1156-3592, Wilson, H.L. orcid.org/0000-0002-7892-3425 et al. (3 more authors) (2019) Hif-1α-Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish. Journal of Immunology, 202 (2). pp. 494-502. ISSN 0022-1767
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license. https://creativecommons.org/licenses/by/4.0/ |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Mar 2019 15:13 |
Last Modified: | 18 Mar 2019 15:13 |
Status: | Published |
Publisher: | American Association of Immunologists |
Refereed: | Yes |
Identification Number: | 10.4049/jimmunol.1801139 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140233 |