PUBLICATION

Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish

Authors
Parikka, M., Hammarén, M.M., Harjula, S.K., Halfpenny, N.J., Oksanen, K.E., Lahtinen, M.J., Pajula, E.T., Iivanainen, A., Pesu, M., and Rämet, M.
ID
ZDB-PUB-121012-8
Date
2012
Source
PLoS pathogens   8(9): e1002944 (Journal)
Registered Authors
Keywords
Zebrafish, Mycobacterium tuberculosis, Tuberculosis, Granulomas, Lymphocytes, Bacterial pathogens, Immune response, Kidneys
MeSH Terms
  • Disease Progression
  • Humans
  • Mycobacterium Infections, Nontuberculous/immunology*
  • Mycobacterium Infections, Nontuberculous/microbiology*
  • Mycobacterium Infections, Nontuberculous/mortality
  • Granulocytes/immunology
  • Granulocytes/radiation effects
  • Mycobacterium marinum/physiology*
  • Lymphocytes/immunology
  • Lymphocytes/radiation effects
  • Tuberculosis/immunology
  • Tuberculosis/microbiology
  • Animals
  • Gamma Rays
  • Zebrafish*
  • Disease Models, Animal
  • Monocytes/immunology
  • Monocytes/radiation effects
  • Immunosuppression Therapy*
(all 19)
PubMed
23028333 Full text @ PLoS Pathog.
Abstract

The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (~35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5?10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz2TgTransgenic Insertion
    hu1999
      Point Mutation
      zdf8TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        Human Disease Fish Conditions Evidence
        tuberculosisWTbacterial treatment: Mycobacterium marinumTAS
        1 - 1 of 1
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        Sequence Targeting Reagents
        No data available
        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        GFPEFGGFP
        1 - 2 of 2
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        Mapping
        No data available