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
-
- Peroxidase/metabolism
- Animals, Genetically Modified
- Disease Models, Animal
- Toll-Like Receptors/metabolism*
- Signal Transduction
- Zebrafish
- Mycobacterium Infections/immunology
- Mycobacterium Infections/metabolism*
- Mycobacterium Infections/microbiology*
- Neutrophils/immunology
- Neutrophils/metabolism
- Receptors, Interleukin-1/metabolism
- Mycobacterium/physiology*
- Animals
- Receptors, Interleukin-8B/metabolism
- Reactive Nitrogen Species/metabolism*
- Interleukin-8/metabolism
- Myeloid Differentiation Factor 88/metabolism
- Tyrosine/metabolism
- PubMed
- 24967596 Full text @ PLoS One
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping