The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling.

Autor:	Yan H; Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX.; Immunology Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX., Walker FC; Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO., Ali A; Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX.; Immunology & Microbiology Graduate Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX., Han H; Department of Pediatrics, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX; and., Tan L; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX., Veillon L; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX., Lorenzi PL; Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX., Baldridge MT; Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO., King KY; Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX.; Immunology Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX.; Immunology & Microbiology Graduate Program, Graduate School of Biomedical Sciences, Baylor College of Medicine, Houston, TX.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Mar 22; Vol. 6 (6), pp. 1754-1765.
DOI:	10.1182/bloodadvances.2021006816
Abstrakt:	Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu