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Updated: Dec 25, 2025
Operating and Biocontainment Procedures of a Facility for Laboratory Mice with a Natural Microbiome: Immunophenotyping Procedure
Published on: December 13, 2024
Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization
Frank Yeung1, Ying-Han Chen2, Jian-Da Lin3
1Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY 10016, USA; Sackler Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY 10016, USA.
Abstract:
Free-living mammals, such as humans and wild mice, display heightened immune activation compared with artificially maintained laboratory mice. These differences are partially attributed to microbial exposure as laboratory mice infected with pathogens exhibit immune profiles more closely resembling that of free-living animals. Here, we examine how colonization by microorganisms within the natural environment contributes to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. However, these "rewilded" mice were not infected by pathogens previously implicated in immune activation. Rather, immune system changes were associated with altered microbiota composition with notable increases in intestinal fungi. Fungi isolated from rewilded mice were sufficient in increasing circulating granulocytes. These findings establish a model to investigate how the natural environment impacts immune development and show that sustained fungal exposure impacts granulocyte numbers.
Insights
Wild mice have stronger immune systems due to microbial exposure. Rewilding lab mice boosted their immune cells, particularly granulocytes, by increasing intestinal fungi, not pathogens.
Area of Science:
- Immunology
- Microbiology
- Environmental Science
Background:
- Free-living mammals exhibit greater immune activation than laboratory mice, partly due to microbial exposures.
- Laboratory mice challenged with pathogens show immune profiles similar to wild counterparts, suggesting environmental microbes shape immunity.
Purpose of the Study:
- To investigate how natural environmental microbial colonization influences immune system maturation.
- To determine if releasing inbred laboratory mice into an outdoor enclosure alters their immune profiles.
Main Methods:
- Inbred laboratory mice were released into an outdoor enclosure to simulate natural environmental exposure.
- Immune cell populations, particularly T cell differentiation and circulating granulocytes, were analyzed.
- Microbiota composition, with a focus on intestinal fungi, was assessed.
- Fungi isolated from rewilded mice were used to test their effect on granulocyte numbers.
Main Results:
- Outdoor release enhanced T cell differentiation and increased circulating granulocytes in mice.
- Immune changes were linked to altered gut microbiota, specifically an increase in intestinal fungi, not pathogen infection.
- Fungi isolated from rewilded mice were sufficient to increase circulating granulocyte counts.
Conclusions:
- The natural environment, through microbial colonization, significantly impacts immune system development and maturation.
- Sustained exposure to environmental fungi plays a role in increasing granulocyte numbers.
- This study provides a model for exploring environmental influences on immune development and highlights the role of fungi in modulating immune cell populations.
