ZFIN ID: ZDB-PUB-180710-13
Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
Harjula, S.E., Ojanen, M.J.T., Taavitsainen, S., Nykter, M., Rämet, M.
Date: 2018
Source: Scientific Reports   8: 10360 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/metabolism
  • Disease Models, Animal
  • Fish Diseases/metabolism
  • Fish Diseases/mortality
  • Fish Diseases/pathology*
  • GATA3 Transcription Factor/genetics
  • GATA3 Transcription Factor/metabolism
  • Interferon-gamma/genetics
  • Interferon-gamma/metabolism*
  • Interleukin-10/genetics*
  • Interleukin-10/metabolism
  • Mycobacterium Infections, Nontuberculous/metabolism
  • Mycobacterium Infections, Nontuberculous/mortality
  • Mycobacterium Infections, Nontuberculous/pathology*
  • Mycobacterium marinum/pathogenicity*
  • Point Mutation
  • Survival Rate
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism
  • Th1 Cells/cytology
  • Th1 Cells/immunology
  • Th1 Cells/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 29985419 Full text @ Sci. Rep.
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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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