Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection.
Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection.
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DOI：
10.1038/s41598-018-28511-w
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发表时间：
2018-07-09
影响因子：
4.6
通讯作者：
Rämet M
中科院分区：
文献类型：
--
作者：
Harjula SE;Ojanen MJT;Taavitsainen S;Nykter M;Rämet M
肺结核是世界上最致命的传染病之一，每年造成100多万人伤亡。IL 10抑制Th1型细胞的功能，并且IL 10缺乏与小鼠模型中针对结核分枝杆菌感染的改善的抗性相关。在这里，我们使用M。marinum感染斑马鱼（Danio rerio）作为研究IL 10在宿主抗分枝杆菌反应中的模型。未经挑战，无义il10e46/e46突变体斑马鱼是可育的，表型正常。在慢性分枝杆菌感染后，与对照组相比，il10e46/e46突变体显示出增强的存活率。这与Th细胞标志物cd4 - 1的表达增加和向Th1型免疫应答的转变有关，这通过tbx21和ifng 1的上调表达以及gata 3的下调来证明。此外，在感染后8周，il10e46/e46突变体斑马鱼的促炎细胞因子tnfb和il1b的表达水平降低，这可能表明感染进展较慢。总之，我们的数据表明，IL 10可以削弱对M的免疫防御。通过限制IFNG1反应在斑马鱼中感染marinum。重要的是，我们的研究结果支持了M。作为结核病模型的斑马鱼marinum感染。
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 il10e46/e46 mutant zebrafish were fertile and phenotypically normal. Following a chronic mycobacterial infection, il10e46/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 il10e46/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.
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DOI：
10.4049/jimmunol.181.8.5545
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beamer GL;Flaherty DK;Assogba BD;Stromberg P;Gonzalez-Juarrero M;de Waal Malefyt R;Vesosky B;Turner J
通讯作者：
Turner J
DOI：
10.4049/jimmunol.1202722
发表时间：
2013-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cyktor JC;Carruthers B;Kominsky RA;Beamer GL;Stromberg P;Turner J
通讯作者：
Turner J
影响因子：
6.7
作者：
Hammarén MM;Oksanen KE;Nisula HM;Luukinen BV;Pesu M;Rämet M;Parikka M
通讯作者：
Parikka M
影响因子：
20.3
作者：
Balla, Keir M.;Lugo-Villarino, Geanncarlo;Traver, David
通讯作者：
Traver, David
DOI：
10.4049/jimmunol.1600959
发表时间：
2016-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dee CT;Nagaraju RT;Athanasiadis EI;Gray C;Fernandez Del Ama L;Johnston SA;Secombes CJ;Cvejic A;Hurlstone AF
通讯作者：
Hurlstone AF