Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.

Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase (iNOS). Consequently, to ensure its survival in macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism. Here we report the mechanism underlying this process,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alexander S Davis, Isabelle Vergne, Sharon S Master, George B Kyei, Jennifer Chua, Vojo Deretic
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4f55e8618b2a4359bf13e110c797bafb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4f55e8618b2a4359bf13e110c797bafb
record_format	dspace
spelling	oai:doaj.org-article:4f55e8618b2a4359bf13e110c797bafb2021-11-25T05:46:48ZMechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.1553-73661553-737410.1371/journal.ppat.0030186https://doaj.org/article/4f55e8618b2a4359bf13e110c797bafb2007-12-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.0030186https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase (iNOS). Consequently, to ensure its survival in macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism. Here we report the mechanism underlying this process, whereby mycobacteria affect the scaffolding protein EBP50, which normally binds to iNOS and links it to the actin cytoskeleton. Phagosomes harboring live mycobacteria showed reduced capacity to retain EBP50, consistent with lower iNOS recruitment. EBP50 was found on purified phagosomes, and its expression increased upon macrophage activation, paralleling expression changes seen with iNOS. Overexpression of EBP50 increased while EBP50 knockdown decreased iNOS recruitment to phagosomes. Knockdown of EBP50 enhanced mycobacterial survival in activated macrophages. We tested another actin organizer, coronin-1, implicated in mycobacterium-macrophage interaction for contribution to iNOS exclusion. A knockdown of coronin-1 resulted in increased iNOS recruitment to model latex bead phagosomes but did not increase iNOS recruitment to phagosomes with live mycobacteria and did not affect mycobacterial survival. Our findings are consistent with a model for the block in iNOS association with mycobacterial phagosomes as a mechanism dependent primarily on reduced EBP50 recruitment.Alexander S DavisIsabelle VergneSharon S MasterGeorge B KyeiJennifer ChuaVojo DereticPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 3, Iss 12, p e186 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Alexander S Davis Isabelle Vergne Sharon S Master George B Kyei Jennifer Chua Vojo Deretic Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
description	Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase (iNOS). Consequently, to ensure its survival in macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism. Here we report the mechanism underlying this process, whereby mycobacteria affect the scaffolding protein EBP50, which normally binds to iNOS and links it to the actin cytoskeleton. Phagosomes harboring live mycobacteria showed reduced capacity to retain EBP50, consistent with lower iNOS recruitment. EBP50 was found on purified phagosomes, and its expression increased upon macrophage activation, paralleling expression changes seen with iNOS. Overexpression of EBP50 increased while EBP50 knockdown decreased iNOS recruitment to phagosomes. Knockdown of EBP50 enhanced mycobacterial survival in activated macrophages. We tested another actin organizer, coronin-1, implicated in mycobacterium-macrophage interaction for contribution to iNOS exclusion. A knockdown of coronin-1 resulted in increased iNOS recruitment to model latex bead phagosomes but did not increase iNOS recruitment to phagosomes with live mycobacteria and did not affect mycobacterial survival. Our findings are consistent with a model for the block in iNOS association with mycobacterial phagosomes as a mechanism dependent primarily on reduced EBP50 recruitment.
format	article
author	Alexander S Davis Isabelle Vergne Sharon S Master George B Kyei Jennifer Chua Vojo Deretic
author_facet	Alexander S Davis Isabelle Vergne Sharon S Master George B Kyei Jennifer Chua Vojo Deretic
author_sort	Alexander S Davis
title	Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
title_short	Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
title_full	Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
title_fullStr	Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
title_full_unstemmed	Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
title_sort	mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/4f55e8618b2a4359bf13e110c797bafb
work_keys_str_mv	AT alexandersdavis mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes AT isabellevergne mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes AT sharonsmaster mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes AT georgebkyei mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes AT jenniferchua mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes AT vojoderetic mechanismofinduciblenitricoxidesynthaseexclusionfrommycobacterialphagosomes
_version_	1718414456646533120

Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.

Ejemplares similares