TECHNICAL | PPC101 DECEMBER 2020

Covid-19, Ebola and HIV originated in animals. The Covid-19 pandemic in particular has rightly refocused our attention to the infections of wild animals. Professor Mark Viney from the Department of Evolution, Ecology and Behaviour at the University of Liverpool shares his research on the ‘zoo of infections’ living in our pest rodents and what it could mean for vector control. 

All around us we see pest species going about their daily lives. What we don’t so easily see is that these animals are engaged in a constant battle with parasites and pathogens that are infecting them.

Animals typically carry a myriad of infections – viruses, bacteria, fungi, protozoa, worms and arthropods (ticks, fleas and lice). This zoo of infections is both inside animals (the gut, mouth, nose and genital tract) and on their skin. Infections of people and livestock are very well known, for obvious reasons, but we know far less about the infections of wild animals.

Animals battle these infections using their immune systems. Their vital, protective role can be seen with severely immune-deficient people who need to live in sterile bubbles. Animal immune systems work to control the zoo of infecting organisms, but we also know very little of the immune responses of wild animals.

Our recent work has been studying the immune responses of wild mice, something that has hardly been done before, revealing some surprising things about the lives of these animals.

Immune responses in wild mice

We have studied the immune responses of wild house mice, Mus musculus domesticus. This is the same species as the laboratory mouse, allowing us to compare immune responses in the wild and the lab. We found some remarkable things. To start with, wild mice have short lives: their average age is about seven weeks, so they have to pack a lot into this short time.

We looked at two main parts of the immune response: antibodies and immune cells. Wild mice have many more antibodies in their circulation than their lab cousins. Antibodies are made in response to an infection, so these high levels of antibodies are a sign of the very high level of infection in wild mice; laboratory mice are deliberately protected from infections, and so have much lower antibody levels.

We also looked at immune cells, specifically ‘T cells’ that act directly against infections. Wild mice had lots of active T cells, and many more than laboratory mice, also a sign of the higher infection load in wild animals. Together the quantities of antibodies and T cells in wild mice tell us that they have lots of infections against which they make immune responses.

While antibodies and T cells attack infections, an excessive immune response can be harmful to the individual; this is immunopathology. The immune system uses molecules (called cytokines) to regulate – turn-up or turn-down – immune responses. Wild mice have lower concentrations of cytokines than laboratory mice.

Isn’t this odd? Shouldn’t wild mice with many infections and high immune responses have lots of cytokines too? No - what we think is going on here is that because wild mice have so many infections that they have to damp-down their immune response, achieving a balance of dealing with the infection but not harming themselves; a low level of cytokines is the sign of this damping.

So, wild mice are carefully balancing, making strong enough immune responses against infections, but without harming themselves in the process. In contrast, laboratory mice have essentially no infections and so don’t have to turn-down their immune responses.

Wild and laboratory mice have different immune responses because of the very different places where they live, and because of their very different levels of infection. While lab mice have taught us a lot about the basic functioning of immune systems, they probably aren’t such good models for understanding the immune lives of wild animals.

Wild animal infections

Wild animals are an increasingly important source of human infection. Covid-19 came from bats, Ebola too, and HIV came from primates, and so there is intense interest in better understanding wild animal infections. What infections wild animals actually have also depends on the immune responses they make, which is why it is important to study these responses.

We are now studying the infections of wild urban rodents, using the human Covid-19 pandemic as a natural experiment. Covid-19 is a coronavirus and there are many different types of coronaviruses that normally infect rodents. Indeed, the wild mice whose immune responses we studied were infected with coronaviruses. The Covid-19 pandemic has focused attention on animal viruses infecting people, but we are now asking if the reverse process is happening, where human Covid-19 virus is infecting rodents. Our idea is that with many people infected with Covid-19 many virus particles are being produced in aerosols and in faeces, which might then infect rodents. Cities have dense populations of people and of pest rats and mice, which might be the perfect conditions for a virus to move from people to rodents. To be clear: this is just an idea, and there is no evidence at the moment that this is happening.

We are now sampling urban rodents and testing them for Covid-19 and other coronaviruses. We are looking for these viruses in lung and gut tissue; in blood we’re looking for antibodies to these viruses. This work is one of only a few studies that have looked for these viruses in rodents, which is perhaps surprising given how common they are in cities.

Viruses change all the time. One way that they do this is by recombining, which is where two different viruses merge their genes to make a new virus. This process might have happened when animal viruses moved into people. In urban pest rodents, we are also looking to see if different coronaviruses are recombing with each other.

While wild animals are all around us, and pest species abound in our towns and cities, it is remarkable to think of the daily battle they are fighting against a whole series of infections that constantly assail them. These infections and animals’ responses to them shape the ecology and biology of these species. It is becoming ever more obvious that our own lives are intimately connected with those of wild animals, which emphasises the importance of studying their infections and immune responses.

Further reading

liverpool.ac.uk/evolution

markviney.com

Abolins, S; Lazarou, L; Weldon, L; Hughes, L; King, EC; Drescher, P; Pocock, MJO; Hafalla, JCR; Riley, EM; Viney, ME. (2018) The ecology of immune state in a wild mammal, Mus musculus domesticus. PLoS Biology, 16, e2003538 journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2003538

Viney, ME; Riley, EM. (2017) The immunology of wild rodents: current status and future prospects. Frontiers in Immunology, 8, 1481 frontiersin.org/articles/10.3389/fimmu.2017.01481/full

Abolins, S; King, E; Lazarou, L; Weldon, L; Hughes, L; Drescher, P; Raynes, J; Hafalla, J; Viney, ME; Riley, EM. (2017) The comparative immunology of wild and laboratory mice Mus musculus domesticus. Nature Communications, 8, 14811 nature.com/articles/ncomms14811

Viney, ME. (2018) The gut microbiota of wild rodents – challenges and opportunities. Laboratory Animals, 53, 252-258 journals.sagepub.com/doi/abs/10.1177/0023677218787538

Funding

This work is supported by the Natural Environment Research Council, which is part of UK Research and Innovation.

Source: PPC101