Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection

Abstract Tuberculosis ranks as one of the world’s deadliest infectious diseases causing more than a million casualties annually. IL10 inhibits the function of Th1 type cells, and IL10 deficiency has been associated with an improved resistance against Mycobacterium tuberculosis infection in a mouse m...

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Autores principales:	Sanna-Kaisa E. Harjula, Markus J. T. Ojanen, Sinja Taavitsainen, Matti Nykter, Mika Rämet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78c1723443f04eeab0de7d9debe41c41
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spelling	oai:doaj.org-article:78c1723443f04eeab0de7d9debe41c412021-12-02T15:07:57ZInterleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection10.1038/s41598-018-28511-w2045-2322https://doaj.org/article/78c1723443f04eeab0de7d9debe41c412018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28511-whttps://doaj.org/toc/2045-2322Abstract Tuberculosis ranks as one of the world’s deadliest infectious diseases causing more than a million casualties annually. IL10 inhibits the function of Th1 type cells, and IL10 deficiency has been associated with an improved resistance against Mycobacterium tuberculosis infection in a mouse model. Here, we utilized M. marinum infection in the zebrafish (Danio rerio) as a model for studying Il10 in the host response against mycobacteria. Unchallenged, nonsense il10 e46/e46 mutant zebrafish were fertile and phenotypically normal. Following a chronic mycobacterial infection, il10 e46/e46 mutants showed enhanced survival compared to the controls. This was associated with an increased expression of the Th cell marker cd4-1 and a shift towards a Th1 type immune response, which was demonstrated by the upregulated expression of tbx21 and ifng1, as well as the down-regulation of gata3. In addition, at 8 weeks post infection il10 e46/e46 mutant zebrafish had reduced expression levels of proinflammatory cytokines tnfb and il1b, presumably indicating slower progress of the infection. Altogether, our data show that Il10 can weaken the immune defense against M. marinum infection in zebrafish by restricting ifng1 response. Importantly, our findings support the relevance of M. marinum infection in zebrafish as a model for tuberculosis.Sanna-Kaisa E. HarjulaMarkus J. T. OjanenSinja TaavitsainenMatti NykterMika RämetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sanna-Kaisa E. Harjula Markus J. T. Ojanen Sinja Taavitsainen Matti Nykter Mika Rämet Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
description	Abstract Tuberculosis ranks as one of the world’s deadliest infectious diseases causing more than a million casualties annually. IL10 inhibits the function of Th1 type cells, and IL10 deficiency has been associated with an improved resistance against Mycobacterium tuberculosis infection in a mouse model. Here, we utilized M. marinum infection in the zebrafish (Danio rerio) as a model for studying Il10 in the host response against mycobacteria. Unchallenged, nonsense il10 e46/e46 mutant zebrafish were fertile and phenotypically normal. Following a chronic mycobacterial infection, il10 e46/e46 mutants showed enhanced survival compared to the controls. This was associated with an increased expression of the Th cell marker cd4-1 and a shift towards a Th1 type immune response, which was demonstrated by the upregulated expression of tbx21 and ifng1, as well as the down-regulation of gata3. In addition, at 8 weeks post infection il10 e46/e46 mutant zebrafish had reduced expression levels of proinflammatory cytokines tnfb and il1b, presumably indicating slower progress of the infection. Altogether, our data show that Il10 can weaken the immune defense against M. marinum infection in zebrafish by restricting ifng1 response. Importantly, our findings support the relevance of M. marinum infection in zebrafish as a model for tuberculosis.
format	article
author	Sanna-Kaisa E. Harjula Markus J. T. Ojanen Sinja Taavitsainen Matti Nykter Mika Rämet
author_facet	Sanna-Kaisa E. Harjula Markus J. T. Ojanen Sinja Taavitsainen Matti Nykter Mika Rämet
author_sort	Sanna-Kaisa E. Harjula
title	Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
title_short	Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
title_full	Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
title_fullStr	Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
title_full_unstemmed	Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
title_sort	interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a mycobacterium marinum infection
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/78c1723443f04eeab0de7d9debe41c41
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Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection

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