Elks, P.M. orcid.org/0000-0003-1683-0749, van der Vaart, M., van Hensbergen, V. et al. (5 more authors) (2014) Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model. PLoS One, 9 (6). e100928. ISSN 1932-6203
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Elks et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Keywords: | Animals; Animals, Genetically Modified; Disease Models, Animal; Interleukin-8; Mycobacterium; Mycobacterium Infections; Myeloid Differentiation Factor 88; Neutrophils; Peroxidase; Reactive Nitrogen Species; Receptors, Interleukin-1; Receptors, Interleukin-8B; Signal Transduction; Toll-Like Receptors; Tyrosine; Zebrafish |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Nov 2016 14:43 |
Last Modified: | 28 Nov 2016 14:43 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0100928 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pone.0100928 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107997 |