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Altered immunity of laboratory mice in the natural environment is associated with fungal colonization

Frank Yeung, Ying-Han Chen, View ORCID ProfileJian-Da Lin, Jacqueline M. Leung, Caroline McCauley, Joseph C. Devlin, Christina Hansen, Alex Cronkite, Zac Stephens, Charlotte Drake-Dunn, Kelly V. Ruggles, June L. Round, P’ng Loke, Andrea L. Graham, Ken Cadwell
doi: https://doi.org/10.1101/742387
Frank Yeung
Kimmel Center for Biology and Medicine at the Skirball InstituteSackler Institute of Graduate Biomedical Sciences
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Ying-Han Chen
Kimmel Center for Biology and Medicine at the Skirball Institute
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Jian-Da Lin
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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  • ORCID record for Jian-Da Lin
Jacqueline M. Leung
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA
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Caroline McCauley
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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Joseph C. Devlin
Sackler Institute of Graduate Biomedical SciencesDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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Christina Hansen
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA
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Alex Cronkite
Kimmel Center for Biology and Medicine at the Skirball InstituteDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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Zac Stephens
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Charlotte Drake-Dunn
Kimmel Center for Biology and Medicine at the Skirball Institute
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Kelly V. Ruggles
Division of Translational Medicine, Department of MedicineApplied Bioinformatics Laboratories, New York School of Medicine, New York, NY 10016, USA
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June L. Round
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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P’ng Loke
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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  • For correspondence: Ken.Cadwell@med.nyu.edu Png.Loke@nyumc.org algraham@princeton.edu
Andrea L. Graham
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA
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  • For correspondence: Ken.Cadwell@med.nyu.edu Png.Loke@nyumc.org algraham@princeton.edu
Ken Cadwell
Kimmel Center for Biology and Medicine at the Skirball InstituteDepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA
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  • For correspondence: Ken.Cadwell@med.nyu.edu Png.Loke@nyumc.org algraham@princeton.edu
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Abstract

The immune systems of free-living mammals such as humans and wild mice display a heightened degree of activation compared with laboratory mice maintained under artificial conditions. Here, we demonstrate that releasing inbred laboratory mice into an outdoor enclosure to mimic life in a natural environment alters the state of immunity. In addition to enhancing the differentiation of T cell populations previously associated with pathogen exposure, we found that outdoor release of mice led to an increase in circulating granulocytes. However, rewilded mice were not infected by pathogens previously implicated in immune activation. Rather, changes to the immune system were associated with an altered composition of the microbiota, and fungi isolated from rewilded mice were sufficient to increase granulocytes. These findings establish an experimental procedure to investigate the impact of the natural environment on immune development and identify a role for sustained fungal colonization in determining granulocyte numbers.

One sentence summary Controlled release of laboratory mice into a natural environment changes the composition of the bacterial and fungal microbiota leading to an altered immune system.

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Posted August 21, 2019.
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Altered immunity of laboratory mice in the natural environment is associated with fungal colonization
Frank Yeung, Ying-Han Chen, Jian-Da Lin, Jacqueline M. Leung, Caroline McCauley, Joseph C. Devlin, Christina Hansen, Alex Cronkite, Zac Stephens, Charlotte Drake-Dunn, Kelly V. Ruggles, June L. Round, P’ng Loke, Andrea L. Graham, Ken Cadwell
bioRxiv 742387; doi: https://doi.org/10.1101/742387
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Altered immunity of laboratory mice in the natural environment is associated with fungal colonization
Frank Yeung, Ying-Han Chen, Jian-Da Lin, Jacqueline M. Leung, Caroline McCauley, Joseph C. Devlin, Christina Hansen, Alex Cronkite, Zac Stephens, Charlotte Drake-Dunn, Kelly V. Ruggles, June L. Round, P’ng Loke, Andrea L. Graham, Ken Cadwell
bioRxiv 742387; doi: https://doi.org/10.1101/742387

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