The determinants of measures of immune function in a wild mammal.

Lead Research Organisation: London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases


Animals make immune responses to protect themselves from infections. All animals have infections during their life: being infected is a normal part of life. Animals can be infected internally with viruses, bacteria, protozoa (single-celled animals) and worms and externally with ticks and mites.

Being infected causes harm to an animal because the infections damage and destroy cells and tissue. The immune responses that animals make to get rid of infections require a lot of energy. Therefore, overall, being infected is costly to an animal.
Wild animals have many other challenges in their lives, apart from infections. For example, they have to search for food, which might often not be very abundant. Further, individuals compete with each other for limited amounts of food. Animals also reproduce which is, again, costly in time and energy. Putting this all together means that wild animals live stressful lives. One important aspect of this stress is that animals may not have enough food and energy to make ideal immune responses or to fully invest in reproduction etc. Therefore, wild animals have to make difficult 'decisions' about how to use their limited resources to keep themselves alive and to pass on their genes.

Because of this, within a group of animals, individuals will vary in how good their immune responses are: some will make very strong responses, others very weak responses. We investigated this in a pilot project where we measured the immune responses of wild mice and, indeed, we found that different individuals vary a lot in the immune responses that they make. By comparing the immune responses of wild and laboratory mice we also found that the immune responses of wild mice are quite different to those of their laboratory cousins.

We now want to understand what aspects of a wild mouse's life determines whether it makes a very strong immune response or a very weak immune response. Laboratory studies of animals have identified lots of things that can affect immune response: we want to find out which of these matter, and how much, in wild mice. Some factors that affect immune function are sex (and sex hormones), genetics, season, age and body condition. For example the male hormone testosterone often suppresses immune responses; animals fed low-protein or low-calorie diets often make weaker or slower immune responses.

In our pilot project work we studied wild mice, Mus musculus. We particularly chose this species because this is also the laboratory mouse. There is a very detailed understanding of the immunology of laboratory mice and very many tools and reagents are available to measure their immune responses. This means that we could make very good measures of immune responses of wild mice, far better than we could for almost any other wild animal.

In the work that we are proposing we will undertake a large survey of wild mice in which we will measure their immune function together with many other aspects of their biology including sex, genetics, size, weight, percent body fat, leptin (the 'fat' hormone) concentration, sex hormone concentrations etc. We will then look for associations between these different factors and immune responses, which will therefore tell us what determines the immune responses of mice in the wild.

This will be the first study that will undertake a comprehensive study of immune function in wild mammals. The results will therefore, for the first time, allow us to understand the main controls of the immune responses of wild animals. This work will be relevant to understanding the immune function of other wild mammals and animals. This is important, not least, because immune function and its variation between individuals is important in affecting epidemics of infection and disease in wild populations.

Planned Impact

Who will benefit from this research?
A range of groups will benefit from this research. This includes immunologists, infectious disease biologists, wildlife ecologists, host and pathogen population ecologists and conservation scientists. Depending on our results this work may also be of interest to animal nutritionists, endocrinologists and geneticists. These groups exist principally in academic research communities, but also in other research organisations (charities and QUANGOs) and interest groups, especially those with a focus and interest in wildlife biology, including conservation, especially with the perspective of environmental change. Our work will have this breadth of interest because the work is undertaking a whole-system approach to immune function of wild animals.

Our work will also be of interest to organisations (commercial and non-commercial) with interests in the control and/ or eradication of rodent pest populations. Examples are Rentokil Pest Control (UK) and the National Pest Technicians' Association (NPTA), both of whom Viney has contacts with.

How will they benefit from this research?
Academic interest groups (immunologists, infectious disease biologists and wildlife ecologists and biologists) will benefit from the new knowledge and understanding of immune function and its control in wild populations that this work will generate. Our work and findings are especially important because it will 'translate' results and understanding drawn from controlled laboratory based work to animals in natural environments.

Those groups with interest in the ecology and biology of wild animals and mammals especially those with interest in conservation and anthropogenic effects on animal populations (academic and non-academic) will also benefit from this research by the acquisition of new knowledge and understanding. Our work will also show that field immunology ('ecoimmunology') is possible and powerful and we envisage that our work will therefore stimulate the growth and development of this field.

Rodent pest eradication specialists may benefit from our work by being provided with new knowledge about their target species, from which they may envisage and develop new and alternative means for the control and eradication of rodent populations. Our work wil explain how the environment contributes to immune function; this will lead to the possibility of being able to predict the effect of specific environmental change on rodent populations. This could be used to control a population (or to enhance or sustain it).

What will be done to ensure that they have they opportunity to benefit from this research?
We shall present our results widely in the academic literature, taking care to publish (with cross referencing) in journals with an ecological focus and immunological focus, together with publication in widely read biology journals. In this way we shall make our work fully and widely available to all those who have the potential to benefit from our research. The number and breadth of our publications will be our first measure of our success in this respect. We shall also present our work at as broad range of scientific meetings (e.g. those with infectious disease, ecological, immunological interests) nationally and internationally, to bring our work and its findings to the attention of the users of our research. We will also aim to present the results of our work in NPTA publications.

To bring our work to wide interest groups we will use established forums, particularly the Bristol Festival of Nature which is a public-facing forum for environmental biology. Both Viney and Pocock have previously worked though this forum.


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Description 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 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. Furthermore, 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 also directly relevant to explaining pathogen spill-over 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 have, individually, been shown to constrain or promote immune responses, such as age, sex, infection status, body condition, and other factors. But, whether or not these factors affect immune responses and immune state in wild animals, their relative importance, and how they interact (or don't) is 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.
Exploitation Route Our findings should lead those working with laboratory reared animals to reconsider their findings in terms of what is likely to be happening in real populations of free living animals (including humans).
Sectors Education



Pharmaceuticals and Medical Biotechnology

Description University of Liverpool - Viney 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Immunological expertise to study of immune function in wild mammals
Collaborator Contribution Ecological, genetic and pathogen expertise to study of immune function in wild mammals
Impact Grant applications in process
Start Year 2018
Description A walk on the wild side 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Long interview, currently featured in an article on the role of studies in free living mammals to understand immunbiology
Year(s) Of Engagement Activity 2017
Description Interview with Cassandra Willard, Nature 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I gave an interview to a Nature journalist who is writing an article on the use of "dirty" animals in research as better models for humans. The article is due to be published in late March 2018
Year(s) Of Engagement Activity 2018