The comparative immunology of wild and laboratory mice, Mus musculus domesticus

TLDR

The laboratory mouse is a cornerstone of immunology, yet it remains unclear how well its immune responses mirror those of free‑living mice. This study systematically compared serological, cellular, and functional immune parameters between wild and laboratory mice, revealing that wild mice exhibit a highly activated cellular immune state. Wild mice possess activated myeloid cells absent in laboratory mice, show reduced in‑vitro cytokine responses, and display immune activation driven by high pathogen exposure, providing a comprehensive benchmark for assessing the relevance of laboratory mice as an immunological model.

Abstract

Abstract The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation. Moreover, wild mice have a population of highly activated myeloid cells not present in laboratory mice. By contrast, in vitro cytokine responses to pathogen-associated ligands are generally lower in cells from wild mice, probably reflecting the importance of maintaining immune homeostasis in the face of intense antigenic challenge in the wild. These data provide a comprehensive basis for validating (or not) laboratory mice as a useful and relevant immunological model system.