Harjula, S., Ojanen, M., Taavitsainen, S., Nykter, M., Rämet, M. (2018) Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection. Scientific Reports, 8 (1), 10360. doi:10.1038/s41598-018-28511-w
Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
|Author:||Harjula, Sanna-Kaisa E.1; Ojanen, Markus J. T.1,2; Taavitsainen, Sinja3;|
1Laboratory of Experimental Immunology, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere
2Laboratory of Immunoregulation, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere
3Laboratory of Computational Biology, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere
4Department of Pediatrics, Tampere University Hospital
5Department of Children and Adolescents, Oulu University Hospital
6PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu
|Online Access:||PDF Full Text (PDF, 3.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2018091335621
|Publish Date:|| 2018-09-13
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3141 Health care science
This study was financially supported by the Academy of Finland (M.R., 277495), the Sigrid Juselius Foundation (M.R.), the Jane and Aatos Erkko Foundation (M.R.), the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (M.R.), Competitive State Research Financing of the Expert Responsibility area of Oulu University Hospital (M.R.) and the Tampere Tuberculosis Foundation (M.R., S.-K.H.), the Emil Aaltonen Foundation (S.-K.H), Foundation of the Finnish Anti-Tuberculosis Association (S.-K.H.), the City of Tampere Science Foundation (S.-K.H), the Väinö and Laina Kivi Foundation (S.-K.H.), the Finnish Cultural Foundation, the Central Foundation (S.-K.H.), the Finnish Concordia Fund (S.-K.H.), Orion Research Foundation sr (S.-K.H) and University of Tampere Doctoral Programme in Biomedicine and Biotechnology (M.O.).
|Academy of Finland Grant Number:||
277495 (Academy of Finland Funding decision)
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