PUBLICATION

Mycobacteria Counteract a TLR-Mediated Nitrosative Defense Mechanism in a Zebrafish Infection Model

Authors
Elks, P.M., van der Vaart, M., van Hensbergen, V., Schutz, E., Redd, M.J., Murayama, E., Spaink, H.P., Meijer, A.H.
ID
ZDB-PUB-140627-8
Date
2014
Source
PLoS One   9: e100928 (Journal)
Registered Authors
Elks, Philip, Meijer, Annemarie H., Murayama, Emi, Redd, Michael, Spaink, Herman P., van der Vaart, Michiel
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Interleukin-8/metabolism
  • Mycobacterium/physiology*
  • Mycobacterium Infections/immunology
  • Mycobacterium Infections/metabolism*
  • Mycobacterium Infections/microbiology*
  • Myeloid Differentiation Factor 88/metabolism
  • Neutrophils/immunology
  • Neutrophils/metabolism
  • Peroxidase/metabolism
  • Reactive Nitrogen Species/metabolism*
  • Receptors, Interleukin-1/metabolism
  • Receptors, Interleukin-8B/metabolism
  • Signal Transduction
  • Toll-Like Receptors/metabolism*
  • Tyrosine/metabolism
  • Zebrafish
PubMed
24967596 Full text @ PLoS One
Abstract
Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping