title: Gut microbiota promote hematopoiesis to control bacterial infection.
abstract: The commensal microbiota impacts specific immune cell populations and their functions at peripheral sites, such as gut mucosal tissues. However, it remains unknown whether gut microbiota control immunity through regulation of hematopoiesis at primary immune sites. We reveal that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. Indeed, following systemic infection with Listeria monocytogenes, germ-free and oral-antibiotic-treated mice display increased pathogen burden and acute death. Recolonization of germ-free mice with a complex microbiota restores defects in myelopoiesis and resistance to Listeria. These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Arya
authors.initials: A
authors.lastname: Khosravi
authors.affiliation: Regenerative Medicine Institute and Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Yáñez
authors.affiliation: Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Price
authors.affiliation: Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chow
authors.affiliation: Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Regenerative Medicine Institute and Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: sarkis@caltech.edu.
authors.forename: Sarkis K
authors.initials: SK
authors.lastname: Mazmanian
mesh_terms: D000818:Animals; D058491:Bacterial Load; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006410:Hematopoiesis; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D016019:Survival Analysis