As they dispersed across the world, human populations interacted with deadly, endemic pathogens, suggesting that natural selection has contributed to present-day population differences in immune responses. Yet, despite the critical impact of infectious diseases on human health, how host genetic factors drive population immune variation remains poorly investigated, primarily because of the strong eurocentrism of genomic studies. Among the least studied regions of the world, South America, and the Amazonian tropical rainforest in particular, are also among the harshest environments for human life. Besides adverse climatic conditions, tropical regions harbor one of the world’s highest pathogenic loads; i.e., human pathogenic diversity is ~70% higher in rainforests than in temperate areas, resulting in unusually high mortality. Yet, studies on biological adaptations among communities such as those habiting the Amazon rainforest are currently lacking. Moreover, South American populations offer the unique opportunity to investigate how microbial pathogens introduced through European contact over the last 500 years, many of which had never been encountered before, resulted in recent biological adaptation.
Here, we propose to use a multi-disciplinary approach that combines population genomics, epigenomics, and systems immunology, to determine, in autochthonous populations from the Amazonia, the genetic and evolutionary factors driving biological diversity in immune responses to various pathogenic stimuli. In doing so, the project will bring new data and knowledge on two fundamental questions related to host-microbe interactions: how humans have adapted to pathogens over time, in particular in the understudied ecosystem of the Amazonia, and which mechanisms have contributed to population differences in immune responses against infectious agents.
