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Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
- Source :
-
PloS one [PLoS One] 2014 Jun 26; Vol. 9 (6), pp. e100928. Date of Electronic Publication: 2014 Jun 26 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Animals, Genetically Modified
Disease Models, Animal
Interleukin-8 metabolism
Mycobacterium Infections immunology
Myeloid Differentiation Factor 88 metabolism
Neutrophils immunology
Neutrophils metabolism
Peroxidase metabolism
Receptors, Interleukin-1 metabolism
Receptors, Interleukin-8B metabolism
Signal Transduction
Tyrosine metabolism
Zebrafish
Mycobacterium physiology
Mycobacterium Infections metabolism
Mycobacterium Infections microbiology
Reactive Nitrogen Species metabolism
Toll-Like Receptors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24967596
- Full Text :
- https://doi.org/10.1371/journal.pone.0100928