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

Ogryzko, Nikolay V ; Lewis, Amy ; Wilson, Heather L ; Meijer, Annemarie H ; Renshaw, Stephen A ; Elks, Philip M

The Journal of immunology (1950), 2019-01, Vol.202 (2), p.494-502 [Periódico revisado por pares]

United States: AAI

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Título:
Hif-1α-Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish
Autor: Ogryzko, Nikolay V ; Lewis, Amy ; Wilson, Heather L ; Meijer, Annemarie H ; Renshaw, Stephen A ; Elks, Philip M
Assuntos: Animals ; Animals, Genetically Modified ; Antitubercular Agents - metabolism ; Cells, Cultured ; Clustered Regularly Interspaced Short Palindromic Repeats ; Disease Models, Animal ; Gene Knockout Techniques ; Green Fluorescent Proteins - genetics ; Humans ; Hypoxia - metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Immunity, Innate ; Infectious Disease and Host Response ; Interleukin-1beta - genetics ; Interleukin-1beta - metabolism ; Macrophages - immunology ; Mycobacterium Infections, Nontuberculous - immunology ; Mycobacterium marinum - physiology ; Mycobacterium tuberculosis - physiology ; Nitric Oxide - metabolism ; Tuberculosis - immunology ; Zebrafish
É parte de: The Journal of immunology (1950), 2019-01, Vol.202 (2), p.494-502
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SourceType-Scholarly Journals-1
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P.M.E., S.A.R., and N.V.O. conceived and designed the experiments; P.M.E., N.V.O., and A.L. performed the experiments; P.M.E., N.V.O., H.L.W., A.H.M., and S.A.R. analyzed the data; P.M.E., N.V.O., and S.A.R. wrote the paper.
Descrição: 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 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.
Editor: United States: AAI
Idioma: Inglês

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

Ogryzko, Nikolay V ; Lewis, Amy ; Wilson, Heather L ; Meijer, Annemarie H ; Renshaw, Stephen A ; Elks, Philip M

United States: AAI

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