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Human Immunology through the Lens of Evolutionary Genetics

Lluis Quintana-Murci, Institut Pasteur
Tuesday May 4, 12-1pm
Zoom Link:聽

Abstract:聽Unravelling the contributions of host and environmental factors to inter-individual and inter-population variability in immune responses is crucial to understand immune pathology. There is growing biomedical interest in studies of the variation of the immune response and its determinants in the healthy population 戮 in a strategy known as systems or population immunology. Here, I will present our recent studies aiming to dissect the genetic, non-genetic and evolutionary determinants of immune response variation. The role played by pathogens in shaping human immune diversity is clearly attested by population genetic studies, indicating that immunity and host defense functions are among those most frequently subject to natural selection. Notably, we have shown that population adaptation to novel pathogen pressures can be facilitated by the acquisition, via admixture, of advantageous alleles from local 鈥渁dapted鈥� populations, such as Neanderthals or modern humans. I will also discuss our work on how genetic variation affects the diversity of molecular phenotypes (i.e., gene expression-eQTL, alternative splicing-sQTL, and DNA methylation-meQTL), and highlight the importance of inferring the causality behind the detected associations between genetic, epigenetic and transcriptional variation. Finally, I will present our most recent data on how adopting an evolutionary genetics approach can inform the history of human exposure to major infectious diseases, such as malaria and tuberculosis. The integration of population genetics and systems immunology thus holds great promise for the increased understanding of the factors driving immune response variation between individuals and populations, with impacts on infectious disease risk.