Using immune cell repertoires to identify pathogen threats

Wild animals live with a myriad of infections - viruses, bacteria, fungi, worms. The harm that these infections cause and the costly efforts animals make to resist these infections affects their ecology and the evolution. So, if we want to properly understand wild animals, we also need to know what infections they have and what immune responses they make against them.

Animal infections also matter directly to humans because they can sometimes jump into humans and then transmit among people directly, so-called zoonoses. The recent COVID pandemic is the most recent example of a zoonosis, in this case with a virus coming from bats. Predicting future zoonoses is another reason why we need to know the infections of wild animals.

But, it is really quite difficult to find out what infections wild animals actually have. While we've lots of specific tests for common infections of humans, livestock and pets these often don't work with wild animals. Our long term vision to solve this problem is to use wild animals' immune cells to find out what infections wild animals have. Here we would harness what immune systems have evolved to do so well: to look very carefully for pathogens everywhere inside an animal. Specifically, when an animal makes an immune response, its immune cells take small bits of the pathogen to then generate a very targeted response. There are different genetic types of immune cells, one for each different pathogen, so that individual animals have a very large collection of different immune cell types. By collecting these cells and sequencing the gene that makes them specific for a pathogen, there is the potential to identify the pathogen infecting the animals.

In the work we are now proposing we want to take the first step on this path: to look at the diversity of immune cell specificity genes in a wild animal, specifically wild mice. We already know that wild mouse immune responses are quite different to those of lab mice, so we expect to see a new pattern of immune cell types in wild mice. We expect the wild animals to have a more diverse set of immune cells than lab mice, because wild mice are infected with more, diverse infections. We will also see to what extent different individual wild mice share immune cell types; such sharing would be evidence that different individuals have the same infection.

The work we're proposing is "blue skies" - that is to have a first look at immune cell diversity in wild animals to see what we find. But, we are doing this with the longer term vison of using this method to study wild animal infections and immune responses, to better understand wild animal ecology, but to also use this to survey wild animals for infections and the next zoonosis that could lead to a global pandemic.