PUBLICATION

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

Authors
Harjula, S.E., Ojanen, M.J.T., Taavitsainen, S., Nykter, M., Rämet, M.
ID
ZDB-PUB-180710-13
Date
2018
Source
Scientific Reports   8: 10360 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Point Mutation
  • Fish Diseases/metabolism
  • Fish Diseases/mortality
  • Fish Diseases/pathology*
  • Interleukin-10/genetics*
  • Interleukin-10/metabolism
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Mycobacterium Infections, Nontuberculous/metabolism
  • Mycobacterium Infections, Nontuberculous/mortality
  • Mycobacterium Infections, Nontuberculous/pathology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • GATA3 Transcription Factor/genetics
  • GATA3 Transcription Factor/metabolism
  • Interferon-gamma/genetics
  • Interferon-gamma/metabolism*
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism
  • Survival Rate
  • Th1 Cells/cytology
  • Th1 Cells/immunology
  • Th1 Cells/metabolism
  • Animals
  • Zebrafish
  • Mycobacterium marinum/pathogenicity*
  • Disease Models, Animal
(all 27)
PubMed
29985419 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
Figure Gallery (2 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTbacterial treatment by injection: Mycobacterium marinumPrim-5 to Day 6
WTbacterial treatment by injection: Mycobacterium marinumAdult
WTbacterial treatment by injection: Mycobacterium marinumAdult
WTbacterial treatment by injection: Mycobacterium marinumAdult
il10e46/e46standard conditionsAdult
il10e46/e46standard conditionsAdult
il10e46/e46standard conditionsAdult
il10e46/e46bacterial treatment by injection: Mycobacterium marinumPrim-5 to Day 6
il10e46/e46bacterial treatment by injection: Mycobacterium marinumAdult
il10e46/e46bacterial treatment by injection: Mycobacterium marinumAdult
1 - 10 of 17
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
e46
    		Point Mutation
    1 - 1 of 1
    Show
    Human Disease / Model
    Human Disease Fish Conditions Evidence
    tuberculosisWTbacterial treatment by injection: Mycobacterium marinumTAS
    1 - 1 of 1
    Show
    Sequence Targeting Reagents
    No data available
    Fish
    Fish
    il10e46/e46
    WT
    1 - 2 of 2
    Show
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Harjula, S.E., Ojanen, M.J.T., 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. 8:10360.