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Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Authors :
Elks PM
van der Vaart M
van Hensbergen V
Schutz E
Redd MJ
Murayama E
Spaink HP
Meijer AH
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.

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