The PathoNat project aims to delineate the genetic and epigenetic factors driving immune variation in Amazonian communities across two host-environment interfaces: the rainforest and the urban environment. In doing so, we will bring new data and knowledge on two fundamental questions related to host-microbe interactions: how humans have adapted to pathogens over time, and which mechanisms have contributed to population differences in immune responses.
To do so, we will measure the transcriptomic profiles of resting and stimulated PBMCs at single cell resolution (4h stimulation with BCG, IFNa, & Cytostim, to capture early anti-bacterial & antiviral response, as well a general adaptive immune responses) 100 forest-based Native Americans from the Peruvian Amazon (shawi communities) and 100 urban-based ‘Mestizos’ (i.e., admixed individuals) from Yurimaguas.
we will also capture chromatin accessibility profiles at basal state to assess the epigentic mechanisms mediating the impact of environmental factors (pathogen exposures, hygiene practices, subsistence mode, habitat, etc…) on immune response variation.