Maternally infection promotes offspring tissue-specific immune fitness

Mammals evolved in the face of pathogen exposure, the vast majority of these encounters resulting in asymptomatic or mild infections. How these constitutive exposures at specific developmental stages impact the host immune system for the long term remains poorly understood. Here we show that maternally restricted, mild infections, can have a permanent and tissue-specific impact on the offspring immunity. This imprinting is associated with a selective increase of Th17 cells within the gut, but not other compartment, and results from enhanced tonic responses to the microbiota. Mechanistically, we found that IL-6 produced by the mother during infection can directly act on fetus intestinal epithelial cells, leading to long-term alteration in chromatin and transcriptomic profiles in intestinal epithelial cells. As such at the adult stage, offspring display enhanced protective responses to oral infections. Together this work proposes that maternal infections can be coopted during fetal development as a mean to promote long-term tissue-specific immune fitness in offspring. Examiniation of epithelial cells and whole tissue through RNA-seq, ATAC-seq and single cell RNA-seq in mice born to mothers treated with control, YopM or IL-6.