A lesson from the wild: The natural state of eosinophils is Ly6G^hi

Abstract

With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non‐laboratory, uncontrolled conditions, we exploit a free‐living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low‐dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context – alongside more mechanistic laboratory experiments – in order to capture the entirety of immune phenotypes and functions.

In-depth comparison of human serous cavity resident macrophages and dendritic cells to their murine counterparts

“…The capture and study of wild house mice from the Isle of May off the coast of Scotland has been described and data reanalyzed from this previous study in order to focus on peritoneal macrophages 35 . Maturity index was defined as a relative age estimate base on the first principal component of a PCA including body length, tail length, weight, and dry eye lens weight.…”

“…We wondered if peritoneal macrophages in mice might drift toward the F4/80 int CD206 + phenotype characterized by lack of Gata6 expression if they were living in an unrestricted natural environment, rather than a specific pathogen-free environment. To examine this possibility, we profiled peritoneal macrophages in house mice, Mus musculus domesticus, that were captured from the wild on the Isle of May off the east coast of Scotland, UK 35 . Analysis of wild-caught mice allowed accounting for real-world pathogens, while also incorporating social behavior, dietary variations, ambient temperature, and seasonal changes that might affect physiology but are not modeled in the laboratory.…”

Embracing nature’s complexity: Immunoparasitology in the wild

“…At the far end of the spectrum, free-living populations of Mus musculus are being studied in their natural environments. In some studies these mice associate closely with human habitation [ 31 ], whilst in others they are relatively independent of anthropogenic influences, as is the case on sparsely or uninhabited islands such as Skokholm [ 32 ] and the Isle of May [ [33] , [34] , [35] ]. Pet shop mice have also served as study system to look at the immune system in a less controlled environment [ 36 , 37 ].…”

“…Without a particular emphasis on the infectious agents involved, the detailed study of immune cells in feral house mice has contributed enormously to our appreciation that the immune system of naïve laboratory mice is indeed naïve, in that it is more akin to the immune system of a newborn than that of an adult human [ 36 ]. The difference in phenotype and abundance of certain immune cells or cell subsets in wild house mice has been shown for T cells [ 31 , 36 ], B cells, myeloid cells [ 31 ] including eosinophils [ 35 ], and NK cells [ 31 , 57 ]. Antigenic exposure is deemed one of the main drivers of these changes, although the immune variation observed in wild mice is likely the result of a more complex network of influencing factors.…”

“…Beyond the analysis of CD8 + T cells in cervical tissue [ 36 ] and of eosinophils in peritoneal exudate [ 35 ] of wild mice, the non-lymphoid tissue distribution and phenotype of immune cells in wild mice living with multiple infections is as yet unexplored. The classical yet debated classification of Type 1 and Type 2 responses with their respective markers would be an ideal candidate to explore in house mice living under natural conditions.…”