دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.
المؤلفون: Taylor GA; Geriatric Research, Education, and Clinical Center, VA Health Care Center, Durham, North Carolina, United States of America.; Departments of Medicine, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United States of America.; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America., Huang HI; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America., Fee BE; Geriatric Research, Education, and Clinical Center, VA Health Care Center, Durham, North Carolina, United States of America., Youssef N; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America., Jewell ML; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America., Cantillana V; Departments of Medicine, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United States of America., Schoenborn AA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Rogala AR; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Buckley AF; Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America., Feng CG; Department of Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, Australia., Vallance BA; Department of Pediatrics, Division of Gastroenterology, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada., Gulati AS; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Hammer GE; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2020 May 26; Vol. 16 (5), pp. e1008553. Date of Electronic Publication: 2020 May 26 (Print Publication: 2020).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Citrobacter rodentium/*immunology , Colon/*immunology , Enterobacteriaceae Infections/*immunology , GTP-Binding Proteins/*deficiency , Inflammatory Bowel Diseases/*immunology , Monocytes/*immunology, Animals ; Colon/microbiology ; Colon/pathology ; Enterobacteriaceae Infections/genetics ; Enterobacteriaceae Infections/pathology ; GTP-Binding Proteins/immunology ; Inflammatory Bowel Diseases/genetics ; Inflammatory Bowel Diseases/microbiology ; Inflammatory Bowel Diseases/pathology ; Mice ; Mice, Knockout ; Monocytes/microbiology ; Monocytes/pathology ; Mucous Membrane/immunology ; Mucous Membrane/microbiology ; Mucous Membrane/pathology
مستخلص: 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.
Competing Interests: I have read the journal's policy and have the following competing interests: B.A.V. is the Children with Intestinal and Liver Disorders (C.H.I.L.D.) Foundation Chair in Pediatric Gastroenterology.
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معلومات مُعتمدة: R21 AI135398 United States AI NIAID NIH HHS; I01 BX002369 United States BX BLRD VA; R01 AI145929 United States AI NIAID NIH HHS; R01 AI145930 United States AI NIAID NIH HHS; R01 AI148243 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Ifi1 protein, mouse)
EC 3.6.1.- (GTP-Binding Proteins)
تواريخ الأحداث: Date Created: 20200527 Date Completed: 20200721 Latest Revision: 20240426
رمز التحديث: 20240426
مُعرف محوري في PubMed: PMC7274479
DOI: 10.1371/journal.ppat.1008553
PMID: 32453761
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1008553