Predicting an animal's immune response based on its genetic data
A new way of selecting animals based on their immune response with the aim of more sustainable production
University of Liège
What if cattle were selected not only for their productivity, but also for their resistance to disease? A study conducted by a team of scientists combining systemic immunology, genomics and machine learning provides a better understanding of what shapes animals' immunity, even before they fall ill. .
Producing animal-based foodstuffs while using fewer synthetic inputs (such as antibiotics) is a major challenge for modern agriculture. To achieve this, we need to understand why some animals are more resistant to infection than others and how much of this is due to their genes, age, season, or rearing conditions. The approach known as "Systems Immunology" – which aims to measure many parameters simultaneously to obtain a dynamic and interconnected overview – is often used in humans, but remains rare in animals. And this is precisely what the recently published study sought to address.
246 calves and more than 200 immune parameters
The scientific team, composed of researchers from the Immunology-Vaccinology Laboratory at the University of Liège, as well as members of the Walloon Breeders' Association, worked on a sample of 246 male Blanc-Bleu-Belge calves that were monitored at the Bovine Selection Centre in Ciney under conditions that were as standardised as possible. "Two blood samples were taken 28 days apart," explains Laurent Gillet, veterinary doctor and immunologist at ULiège. "These samples enabled us to draw up a real immune 'dashboard' for each animal at two points in time."
"The animals were also genotyped," says Carole Charlier, veterinarian and geneticist at ULiège. This means that we collected a large amount of genetic information characterising the specific genetic variation of an animal, using a strategy that combines DNA chips and whole genome sequencing to achieve a very high-resolution analysis (millions of variants).
The environment, but not only
Non-genetic factors, such as seasonality, explain much of the overall immune variability observed between animals. In other words, two calves may have different immune profiles simply because they were not sampled at the same time of year, or because their recent history (housing conditions, farm of origin, etc.) is not identical. "This result is important," Laurent Gillet continues, "because if we want to compare animals or evaluate the effect of an intervention, we must take these environmental parameters into account, otherwise we risk attributing to genes what is in fact due to the season, the age of the animal, farming practices or other variables." In addition, the results also show that certain genes have a decisive influence on specific aspects of immunity. In particular, the team identified genetic variations that influence the production of cytokines, key molecules in the immune response. Cytokines orchestrate inflammation, the activation of defences or, conversely, a return to calm.
The researchers trained a predictive model linking genetic data and cytokine responses. "The aim is not to predict the future perfectly, but to test an idea: can we use a genetic profile to estimate part of future immune behaviour? The results show that this is possible to a certain extent, paving the way for the judicious use of these tools for selection and health management, provided that the cohorts are further expanded and validated on other populations.
Thanks to this study, researchers have been able to develop a model capable of estimating an animal's immune response based on its genetic data. This work paves the way for the selection of cattle that are naturally more resistant to disease, which could reduce the use of antibiotics and other molecules and improve the sustainability of livestock farming. "The idea is not to produce high-performing but fragile animals that can only survive in ultra-controlled conditions, but to keep in mind adaptation to the real environment. We also want to be able to identify certain genetic profiles that are particularly sensitive," concludes Laurent Gillet. The next step will be to look at other breeds and other factors.
Journal
Nature Communications
Article Title
Genetic and non-genetic factors distinctly shape the variation of the immune response in cattle
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