Foetal immune development is modulated by challenges of the modern environment, such as high maternal stress perception. In turn, prenatal stress increases the risk for infections later in life of the offspring. Surprisingly, the offspring’s sex has been overlooked in most of these studies, despite the well-known sex disparities in infection risks. We aim to close this gap in knowledge. We hypothesize that prenatal stress exposure causes variation of the sex-specific disease tolerance to pathogens in offspring. differentially affects immunity to pathogens throughout postnatal life of male and female offspring. We also hypothesize that such variations of sex-specific immunity to pathogens segues into evolutionary trade-offs. We will use influenza A virus-induced infection in a mouse model, which we established during the first funding period. The translational relevance of these preclinical insights will be tested using data and bio-samples from children born into a prospectively designed pregnancy study. In synergy with other projects of the RU 5068, our focus lies on dissecting distinct innate and adaptive immune pathways and their modulation by sex and steroid hormones. Since genes encoded by the X chromosome may be affected by prenatal stress, we plan to use expertise within the RU 5068 to investigate this aspect. Collectively, this project will provide valuable insights into the mechanisms underlying prenatally imprinted, sex-specific susceptibilities to infections throughout life. Our study holds the potential to specify health guidelines and vaccination regimen for specific sex and age groups which have a greater susceptibility to infections.

DFG Programme Research Units

Subproject of FOR 5068:  Sex differences in immunity