Mind the gap: unraveling immune variation across the global north/south populations with high-dimensional approaches

Abstract

This thesis investigates the structure and consequences of human immune variation, emphasizing understudied populations in the Global South. By leveraging high-dimensional immunological analyses—including mass cytometry and transcriptomics—the work elucidates how environmental factors shape immune phenotypes and responses to perturbations. The thesis characterizes rural-urban immune gradients, revealing conserved immunological signatures across continents, and identifies cell subsets associated with parasite control in malaria and response to hookworm infection in both naïve and pre-exposed individuals. This work argues for a broader inclusion of populations to generate immunological reference datasets, which may facilitate generative AI applications to simulate immune responses in unseen populations and perturbations. Collectively, the work advances our understanding of immune diversity and its implications for disease susceptibility, vaccine efficacy, and therapeutic development across global populations.