دورية أكاديمية
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Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.

التفاصيل البيبلوغرافية
العنوان: Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.
المؤلفون: Littmann ER; The Duchossois Family Institute, University of Chicago, Chicago, IL, USA., Lee JJ; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Denny JE; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Alam Z; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Maslanka JR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Zarin I; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Matsuda R; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA., Carter RA; Lucille Castori Center, Molecular Microbiology Core Facility, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Susac B; Lucille Castori Center, Molecular Microbiology Core Facility, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Saffern MS; Lucille Castori Center, Molecular Microbiology Core Facility, Sloan-Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fett B; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Mattei LM; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Bittinger K; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Abt MC; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Michael.abt@pennmedicine.upenn.edu.
المصدر: Nature communications [Nat Commun] 2021 Feb 02; Vol. 12 (1), pp. 755. Date of Electronic Publication: 2021 Feb 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Clostridioides difficile/*pathogenicity, Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Clostridium Infections/immunology ; Clostridium Infections/metabolism ; Feces/microbiology ; Forkhead Transcription Factors/metabolism ; Homeodomain Proteins/metabolism ; Inflammation/immunology ; Inflammation/metabolism ; Mice ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
مستخلص: Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1 -/- mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4 + Foxp3 + T-regulatory cells, but not B cells or CD8 + T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.
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معلومات مُعتمدة: P30 CA008748 United States CA NCI NIH HHS; R00 AI125786 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
0 (Homeodomain Proteins)
128559-51-3 (RAG-1 protein)
تواريخ الأحداث: Date Created: 20210203 Date Completed: 20210301 Latest Revision: 20230128
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7854624
DOI: 10.1038/s41467-020-20793-x
PMID: 33531483
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-020-20793-x