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, Yi Fulmer, Bo Shopsin, Kelly V. Ruggles, June L. Round, P'ng Loke, Andrea L. Graham, Ken Cadwell

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)809-822.e6
JournalCell Host and Microbe
Issue number5
StatePublished - May 13 2020

All Science Journal Classification (ASJC) codes

  • Virology
  • Parasitology
  • Microbiology


  • Aspergillus
  • fungi
  • granulocytes
  • laboratory mice
  • mesocosm
  • microbiota
  • mycobiota
  • neutrophils
  • rewilding
  • wild mice


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