Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.

IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscor...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gregory A Taylor, Hsin-I Huang, Brian E Fee, Nourhan Youssef, Mark L Jewell, Viviana Cantillana, Alexi A Schoenborn, Allison R Rogala, Anne F Buckley, Carl G Feng, Bruce A Vallance, Ajay S Gulati, Gianna E Hammer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0f551c4084a24ce09013efa7ff036e98
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0f551c4084a24ce09013efa7ff036e98
record_format	dspace
spelling	oai:doaj.org-article:0f551c4084a24ce09013efa7ff036e982021-12-02T19:59:38ZIrgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.1553-73661553-737410.1371/journal.ppat.1008553https://doaj.org/article/0f551c4084a24ce09013efa7ff036e982020-05-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1008553https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates immunity to microbes relevant to intestinal inflammation. Here we find that loss of Irgm1 confers marked susceptibility to Citrobacter rodentium, a noninvasive intestinal pathogen that models inflammatory responses to intestinal bacteria. Irgm1-deficient mice fail to control C. rodentium outgrowth in the intestine, leading to systemic pathogen spread and host mortality. Surprisingly, susceptibility due to loss of Irgm1 function was not linked to defective intracellular killing of C. rodentium or exaggerated inflammation, but was instead linked to failure to remodel specific colon lamina propria (C-LP) myeloid cells that expand in response to C. rodentium infection and are essential for C. rodentium immunity. Defective immune remodeling was most striking in C-LP monocytes, which were successfully recruited to the infected C-LP, but subsequently underwent apoptosis. Apoptotic susceptibility was induced by C. rodentium infection and was specific to this setting of pathogen infection, and was not apparent in other settings of intestinal inflammation. These studies reveal a novel role for Irgm1 in host defense and suggest that deficiencies in survival and remodeling of C-LP myeloid cells that control inflammatory intestinal bacteria may underpin IBD pathogenesis linked to IRGM dysfunction.Gregory A TaylorHsin-I HuangBrian E FeeNourhan YoussefMark L JewellViviana CantillanaAlexi A SchoenbornAllison R RogalaAnne F BuckleyCarl G FengBruce A VallanceAjay S GulatiGianna E HammerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 16, Iss 5, p e1008553 (2020)
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 Gregory A Taylor Hsin-I Huang Brian E Fee Nourhan Youssef Mark L Jewell Viviana Cantillana Alexi A Schoenborn Allison R Rogala Anne F Buckley Carl G Feng Bruce A Vallance Ajay S Gulati Gianna E Hammer Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
description	IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates immunity to microbes relevant to intestinal inflammation. Here we find that loss of Irgm1 confers marked susceptibility to Citrobacter rodentium, a noninvasive intestinal pathogen that models inflammatory responses to intestinal bacteria. Irgm1-deficient mice fail to control C. rodentium outgrowth in the intestine, leading to systemic pathogen spread and host mortality. Surprisingly, susceptibility due to loss of Irgm1 function was not linked to defective intracellular killing of C. rodentium or exaggerated inflammation, but was instead linked to failure to remodel specific colon lamina propria (C-LP) myeloid cells that expand in response to C. rodentium infection and are essential for C. rodentium immunity. Defective immune remodeling was most striking in C-LP monocytes, which were successfully recruited to the infected C-LP, but subsequently underwent apoptosis. Apoptotic susceptibility was induced by C. rodentium infection and was specific to this setting of pathogen infection, and was not apparent in other settings of intestinal inflammation. These studies reveal a novel role for Irgm1 in host defense and suggest that deficiencies in survival and remodeling of C-LP myeloid cells that control inflammatory intestinal bacteria may underpin IBD pathogenesis linked to IRGM dysfunction.
format	article
author	Gregory A Taylor Hsin-I Huang Brian E Fee Nourhan Youssef Mark L Jewell Viviana Cantillana Alexi A Schoenborn Allison R Rogala Anne F Buckley Carl G Feng Bruce A Vallance Ajay S Gulati Gianna E Hammer
author_facet	Gregory A Taylor Hsin-I Huang Brian E Fee Nourhan Youssef Mark L Jewell Viviana Cantillana Alexi A Schoenborn Allison R Rogala Anne F Buckley Carl G Feng Bruce A Vallance Ajay S Gulati Gianna E Hammer
author_sort	Gregory A Taylor
title	Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
title_short	Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
title_full	Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
title_fullStr	Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
title_full_unstemmed	Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
title_sort	irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen citrobacter rodentium.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/0f551c4084a24ce09013efa7ff036e98
work_keys_str_mv	AT gregoryataylor irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT hsinihuang irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT brianefee irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT nourhanyoussef irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT markljewell irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT vivianacantillana irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT alexiaschoenborn irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT allisonrrogala irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT annefbuckley irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT carlgfeng irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT bruceavallance irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT ajaysgulati irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium AT giannaehammer irgm1deficiencyleadstomyeloiddysfunctionincolonlaminapropriaandsusceptibilitytotheintestinalpathogencitrobacterrodentium
_version_	1718375704037425152

Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.

Ejemplares similares