Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization

Cell Host Microbe. 2020 May 13;27(5):809-822.e6. doi: 10.1016/j.chom.2020.02.015. Epub 2020 Mar 24.


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.

Keywords: Aspergillus; fungi; granulocytes; laboratory mice; mesocosm; microbiota; mycobiota; neutrophils; rewilding; wild mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy-Related Proteins / genetics
  • CD8-Positive T-Lymphocytes
  • Environment*
  • Feces / microbiology
  • Female
  • Fungi / genetics
  • Fungi / growth & development*
  • Fungi / isolation & purification
  • Fungi / physiology*
  • Gastrointestinal Microbiome / immunology*
  • Granulocytes / immunology
  • Immune System
  • Intestines / microbiology
  • Intestines / pathology
  • Lymphocytes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobiome / immunology
  • Mycobiome / physiology
  • Nod2 Signaling Adaptor Protein / genetics


  • Atg16l1 protein, mouse
  • Autophagy-Related Proteins
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse