학술논문
Rewilding of laboratory mice enhances granulopoiesis and immunity through intestinal fungal colonization.
Document Type
Academic Journal
Author
Chen YH; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.; Yeung F; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.; Lacey KA; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.; Zaldana K; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.; Lin JD; Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei City, Taiwan.; Bee GCW; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.; McCauley C; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.; Barre RS; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.; Liang SH; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.; Hansen CB; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.; Downie AE; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.; Tio K; Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.; Weiser JN; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.; Antimicrobial-Resistant Pathogens Program, New York University Grossman School of Medicine, New York, NY 10016, USA.; Torres VJ; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.; Antimicrobial-Resistant Pathogens Program, New York University Grossman School of Medicine, New York, NY 10016, USA.; Bennett RJ; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.; Loke P; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.; Graham AL; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.; Cadwell K; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Source
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE
Subject
Language
English
Abstract
The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause of this species-specific difference is unclear. We previously demonstrated that laboratory mice released into a seminatural environment, referred to as rewilding, display an increase in blood granulocytes that is associated with expansion of fungi in the gut microbiota. Here, we find that tonic signals from fungal colonization induce sustained granulopoiesis through a mechanism distinct from emergency granulopoiesis, leading to a prolonged expansion of circulating neutrophils that promotes immunity. Fungal colonization after either rewilding or oral inoculation of laboratory mice with Candida albicans induced persistent expansion of myeloid progenitors in the bone marrow. This increase in granulopoiesis conferred greater long-term protection from bloodstream infection by gram-positive bacteria than by the trained immune response evoked by transient exposure to the fungal cell wall component β-glucan. Consequently, introducing fungi into laboratory mice may restore aspects of leukocyte development and provide a better model for humans and free-living mammals that are constantly exposed to environmental fungi.