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
  • Neutrophils/immunology
  • Neutrophils/metabolism
  • Peroxidase/metabolism
  • Mycobacterium Infections/immunology
  • Mycobacterium Infections/metabolism*
  • Mycobacterium Infections/microbiology*
  • Animals
  • Receptors, Interleukin-8B/metabolism
  • Animals, Genetically Modified
  • Signal Transduction
  • Toll-Like Receptors/metabolism*
  • Tyrosine/metabolism
  • Interleukin-8/metabolism
  • Disease Models, Animal
  • Mycobacterium/physiology*
  • Zebrafish
  • Reactive Nitrogen Species/metabolism*
  • Myeloid Differentiation Factor 88/metabolism
  • Receptors, Interleukin-1/metabolism
(all 19)
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
Figure Gallery (10 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
DsRed2nz50Tgbacterial treatmentLong-pecIHC
DsRed2nz50Tgstandard conditionsLong-pecIHC
GFPi114Tgbacterial treatmentPrim-15IHC
GFPi114Tgbacterial treatmentLong-pecIHC
GFPi114TgcontrolLong-pecIHC
GFPi114TgcontrolLong-pecIHC
GFPi114Tgchemical treatment: pharmaceuticalLong-pecIHC
GFPi114Tgbacterial treatmentPrim-25IHC
GFPi114Tgchemical treatment: pharmaceutical, bacterial treatmentLong-pecIHC
GFPi114Tgbacterial treatmentLong-pecIHC
1 - 10 of 22
Show
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu3568
    		Point Mutation
    i114TgTransgenic Insertion
      nz50TgTransgenic Insertion
        t30963
          		Point Mutation
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          cxcl8aMO5-cxcl8aMRPHLNO
          cxcl8b.1MO1-cxcl8b.1MRPHLNO
          1 - 2 of 2
          Show
          Fish
          Fish
          i114Tg
          i114Tg + MO1-cxcl8b.1 + MO5-cxcl8a
          mpxt30963/t30963
          mpxt30963/t30963; i114Tg
          myd88hu3568/hu3568; i114Tg
          nz50Tg
          1 - 6 of 6
          Show
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-nitrotyrosinepolyclonal
            		IgGRabbit
            Ab2-nospolyclonal
              		Rabbit
              1 - 2 of 2
              Show
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              DsRed2EFGDsRed2
              GFPEFGGFP
              1 - 2 of 2
              Show
              Mapping
              No data available
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              Citation
              Elks, P.M., van der Vaart, M., van Hensbergen, V., Schutz, E., Redd, M.J., Murayama, E., Spaink, H.P., Meijer, A.H. (2014) Mycobacteria Counteract a TLR-Mediated Nitrosative Defense Mechanism in a Zebrafish Infection Model. PLoS One. 9:e100928.