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

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 p...

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Autores principales:	Philip M Elks, Michiel van der Vaart, Vincent van Hensbergen, Esther Schutz, Michael J Redd, Emi Murayama, Herman P Spaink, Annemarie H Meijer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df3c36734a6a4d189850266f51994aa3
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spelling	oai:doaj.org-article:df3c36734a6a4d189850266f51994aa32021-11-11T08:21:30ZMycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.1932-620310.1371/journal.pone.0100928https://doaj.org/article/df3c36734a6a4d189850266f51994aa32014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24967596/?tool=EBIhttps://doaj.org/toc/1932-6203Pulmonary 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.Philip M ElksMichiel van der VaartVincent van HensbergenEsther SchutzMichael J ReddEmi MurayamaHerman P SpainkAnnemarie H MeijerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e100928 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philip M Elks Michiel van der Vaart Vincent van Hensbergen Esther Schutz Michael J Redd Emi Murayama Herman P Spaink Annemarie H Meijer Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
description	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.
format	article
author	Philip M Elks Michiel van der Vaart Vincent van Hensbergen Esther Schutz Michael J Redd Emi Murayama Herman P Spaink Annemarie H Meijer
author_facet	Philip M Elks Michiel van der Vaart Vincent van Hensbergen Esther Schutz Michael J Redd Emi Murayama Herman P Spaink Annemarie H Meijer
author_sort	Philip M Elks
title	Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
title_short	Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
title_full	Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
title_fullStr	Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
title_full_unstemmed	Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
title_sort	mycobacteria counteract a tlr-mediated nitrosative defense mechanism in a zebrafish infection model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/df3c36734a6a4d189850266f51994aa3
work_keys_str_mv	AT philipmelks mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT michielvandervaart mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT vincentvanhensbergen mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT estherschutz mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT michaeljredd mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT emimurayama mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT hermanpspaink mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel AT annemariehmeijer mycobacteriacounteractatlrmediatednitrosativedefensemechanisminazebrafishinfectionmodel
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Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

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