Bio-imaging technology for better diagnostic tools
Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
|Title||Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Elks, P.M., van der Vaart M., van Hensbergen V., Schutz E., Redd M.J., Murayama E., Spaink H.P., Meijer A.H.|
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.
|Alternate Journal||PLoS ONE|