Rewilding of laboratory mice enhances granulopoiesis and immunity through intestinal fungal colonization
Year: 2023
Type: article
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.
Source: Science Immunology
Authors: Ying-Han Chen, Frank Yeung, Keenan A. Lacey, Kimberly Zaldana, Jian-Da Lin, Gavyn Chern Wei Bee, Caroline McCauley, Ramya S. Barre, Shen-Huan Liang, Christina B. Hansen, Alexander E. Downie, Kyle Tio, Jeffrey N. Weiser, Victor J. Torres, Richard J. Bennett, P’ng Loke, Andrea L. Graham, Ken Cadwell
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Kenneth Rainin Foundation, National Institutes of Health, NYU Grossman School of Medicine, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Mechanisms of pneumococcal persistence during carriage, Sandy Recovery Ventana Medical Systems Discovery XT, Mechanisms of MRSA intestinal colonization, The role of autophagy gene Atg16L1 in allogeneic hematopoietic stem cell transplantation - Renewal - 1, Interactions between helminth colonization and the gut microbiota, G5790579924, The effects of a wild gut microbiome on mucosal immunity and disease, Mechanisms of fungal involvement during intestinal disease, G9000233264, Mechanisms of Pneumococcal Persistence During Carriage, Redefining the role of autophagy in bacterial disease, Characterization of a commensal enteric virus, Cancer Center Support Grant
OpenAlex ID: W4381801288