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.

The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter-individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection.

The immune function of wild animals has been rather little studied. Wild animals' immune function may differ from that of laboratory bred animals because of their different environments. This idea follows from the concept of resource partitioning in which animals distribute scarce resources to all aspects of life, including to costly immune responses. A logical extension of this idea is that there may be substantial interindividual variation in the immune function of wild animals. To begin to investigate this, we compared the immune function of a laboratory bred mouse strain (C57BL/6, a widely used mouse strain that makes potent immune responses) and wild caught Mus musculus. We found that by most measures of immune function, the wild caught mice had greater immune function. Specifically, wild mice had greater concentrations and more avid antigen-specific IgG responses, as well as higher concentrations of total IgG and IgE, compared with those laboratory bred mice. Moreover, flow cytometric analysis showed a comparatively greater overall level of activation of the cells of the immune system in wild mice. Lastly, we observed that immune function was substantially more variable among wild caught mice than among the laboratory bred mice. The next research challenge is to understand which aspects of an individual animal's life determine its immune function.

Summary 1.Calyptrate flies include numerous species that are disease vectors and have a high nuisance value, notably Musca domestica . Populations are often associated with livestock farms and domestic waste disposal facilities such as landfill, where the accumulating organic matter provides suitable breeding conditions for a range of species. 2. We examined the relationship between fly numbers and weather conditions using a 4-year data set of weekly fly catches from six sites in southern UK, together with meteorological data. The first 3 years were used to develop predictive models, and these were then used to forecast fly populations in the fourth year. The accuracy of these predictions was assessed by comparison with the actual fly catches for that year. Separate models were developed for M. domestica , Calliphora spp. and all calyptrate flies combined. 3. Predictions based only on humidity, temperature and rainfall were strongly correlated with observed data ( r 2 values ranged from 0·52 to 0·84), suggesting that fly population changes are largely driven by the weather rather than by biotic factors. We can forecast fly populations so that control measures need only be deployed when weather conditions are suitable for a fly outbreak, reducing the need for prophylactic insecticide use. 4. Climate change was simulated using the most recent predictions of future temperature increases. Our models predicted substantial increases in fly populations up to 244% by 2080 compared with current levels, with the greatest increases occurring in the summer months. 5. Synthesis and applications. Models developed use weather data to predict populations of pestiferous flies such as M. domestica , which may prove valuable in integrated control programmes. These models predict substantial increases in fly populations in the future under likely scenarios of climate change. If this occurs we may expect considerable increases in the incidence of fly-borne disease.

The immune state of wild animals is largely unknown. Knowing this and what affects it is important in understanding how infection and disease affects wild animals. The immune state of wild animals is also important in understanding the biology of their pathogens, which is directly relevant to explaining pathogen spillover among species, including to humans. The paucity of knowledge about wild animals' immune state is in stark contrast to our exquisitely detailed understanding of the immunobiology of laboratory animals. Making an immune response is costly, and many factors (such as age, sex, infection status, and body condition) have individually been shown to constrain or promote immune responses. But, whether or not these factors affect immune responses and immune state in wild animals, their relative importance, and how they interact (or do not) are unknown. Here, we have investigated the immune ecology of wild house mice—the same species as the laboratory mouse—as an example of a wild mammal, characterising their adaptive humoral, adaptive cellular, and innate immune state. Firstly, we show how immune variation is structured among mouse populations, finding that there can be extensive immune discordance among neighbouring populations. Secondly, we identify the principal factors that underlie the immunological differences among mice, showing that body condition promotes and age constrains individuals’ immune state, while factors such as microparasite infection and season are comparatively unimportant. By applying a multifactorial analysis to an immune system-wide analysis, our results bring a new and unified understanding of the immunobiology of a wild mammal.