University of Oulu

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

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Author: Harjula, Sanna-Kaisa E.1; Ojanen, Markus J. T.1,2; Taavitsainen, Sinja3;
Organizations: 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
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2018091335621
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-09-13
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 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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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 8
Article number: 10360
DOI: 10.1038/s41598-018-28511-w
OADOI: https://oadoi.org/10.1038/s41598-018-28511-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
Subjects:
Funding: 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
Detailed Information: 277495 (Academy of Finland Funding decision)
Dataset Reference: Electronic supplementary material
  https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-018-28511-w/MediaObjects/41598_2018_28511_MOESM1_ESM.pdf
https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-018-28511-w/MediaObjects/41598_2018_28511_MOESM2_ESM.xlsx
https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-018-28511-w/MediaObjects/41598_2018_28511_MOESM3_ESM.xlsx
https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-018-28511-w/MediaObjects/41598_2018_28511_MOESM4_ESM.xlsx
Copyright information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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