IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.

Chlamydial infection of the host cell induces Gamma interferon (IFNgamma), a central immunoprotector for humans and mice. The primary defense against Chlamydia infection in the mouse involves the IFNgamma-inducible family of IRG proteins; however, the precise mechanisms mediating the pathogen's...

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Autores principales:	Munir A Al-Zeer, Hesham M Al-Younes, Peter R Braun, Jens Zerrahn, Thomas F Meyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06ce659de8d347c7b22946df56d30575
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spelling	oai:doaj.org-article:06ce659de8d347c7b22946df56d305752021-11-25T06:17:05ZIFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.1932-620310.1371/journal.pone.0004588https://doaj.org/article/06ce659de8d347c7b22946df56d305752009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19242543/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Chlamydial infection of the host cell induces Gamma interferon (IFNgamma), a central immunoprotector for humans and mice. The primary defense against Chlamydia infection in the mouse involves the IFNgamma-inducible family of IRG proteins; however, the precise mechanisms mediating the pathogen's elimination are unknown. In this study, we identify Irga6 as an important resistance factor against C. trachomatis, but not C. muridarum, infection in IFNgamma-stimulated mouse embryonic fibroblasts (MEFs). We show that Irga6, Irgd, Irgm2 and Irgm3 accumulate at bacterial inclusions in MEFs upon stimulation with IFNgamma, whereas Irgb6 colocalized in the presence or absence of the cytokine. This accumulation triggers a rerouting of bacterial inclusions to autophagosomes that subsequently fuse to lysosomes for elimination. Autophagy-deficient Atg5-/- MEFs and lysosomal acidification impaired cells surrender to infection. Irgm2, Irgm3 and Irgd still localize to inclusions in IFNgamma-induced Atg5-/- cells, but Irga6 localization is disrupted indicating its pivotal role in pathogen resistance. Irga6-deficient (Irga6-/-) MEFs, in which chlamydial growth is enhanced, do not respond to IFNgamma even though Irgb6, Irgd, Irgm2 and Irgm3 still localize to inclusions. Taken together, we identify Irga6 as a necessary factor in conferring host resistance by remodelling a classically nonfusogenic intracellular pathogen to stimulate fusion with autophagosomes, thereby rerouting the intruder to the lysosomal compartment for destruction.Munir A Al-ZeerHesham M Al-YounesPeter R BraunJens ZerrahnThomas F MeyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4588 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Munir A Al-Zeer Hesham M Al-Younes Peter R Braun Jens Zerrahn Thomas F Meyer IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
description	Chlamydial infection of the host cell induces Gamma interferon (IFNgamma), a central immunoprotector for humans and mice. The primary defense against Chlamydia infection in the mouse involves the IFNgamma-inducible family of IRG proteins; however, the precise mechanisms mediating the pathogen's elimination are unknown. In this study, we identify Irga6 as an important resistance factor against C. trachomatis, but not C. muridarum, infection in IFNgamma-stimulated mouse embryonic fibroblasts (MEFs). We show that Irga6, Irgd, Irgm2 and Irgm3 accumulate at bacterial inclusions in MEFs upon stimulation with IFNgamma, whereas Irgb6 colocalized in the presence or absence of the cytokine. This accumulation triggers a rerouting of bacterial inclusions to autophagosomes that subsequently fuse to lysosomes for elimination. Autophagy-deficient Atg5-/- MEFs and lysosomal acidification impaired cells surrender to infection. Irgm2, Irgm3 and Irgd still localize to inclusions in IFNgamma-induced Atg5-/- cells, but Irga6 localization is disrupted indicating its pivotal role in pathogen resistance. Irga6-deficient (Irga6-/-) MEFs, in which chlamydial growth is enhanced, do not respond to IFNgamma even though Irgb6, Irgd, Irgm2 and Irgm3 still localize to inclusions. Taken together, we identify Irga6 as a necessary factor in conferring host resistance by remodelling a classically nonfusogenic intracellular pathogen to stimulate fusion with autophagosomes, thereby rerouting the intruder to the lysosomal compartment for destruction.
format	article
author	Munir A Al-Zeer Hesham M Al-Younes Peter R Braun Jens Zerrahn Thomas F Meyer
author_facet	Munir A Al-Zeer Hesham M Al-Younes Peter R Braun Jens Zerrahn Thomas F Meyer
author_sort	Munir A Al-Zeer
title	IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
title_short	IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
title_full	IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
title_fullStr	IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
title_full_unstemmed	IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.
title_sort	ifn-gamma-inducible irga6 mediates host resistance against chlamydia trachomatis via autophagy.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/06ce659de8d347c7b22946df56d30575
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IFN-gamma-inducible Irga6 mediates host resistance against Chlamydia trachomatis via autophagy.

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