Dynamics and transgenerational inheritance of infection-induced epigenetic traits

Tuberculosis (TB) and COVID-19 have highly variable infection susceptibility patterns, which cannot be explained by genetics or systemic immunity.

We have found that both infections leave epigenetic marks in immune cells, but it is not known how they arise and if they correlate to susceptibility, disease severity, the risk of developing sequelae, or whether the changes can propagate across generations.

Our hypotheses are: 1) During infections such as TB and COVID-19, a tailored, dynamic epigenetic change contributes to infection control. 2) Exosomes convey information from infected cells to the body tissues and across generations to direct epigenetic reprogramming resulting in protection. 3) An aberrant epigenetic landscape, either existing before infection or triggered by the same, can explain susceptibility to infection or infection-induced sequelae.

To test these hypotheses, we create a platform for data-driven, machine learning-assisted exploration of epigenomic data from unique clinical materials and experimental assays.

The objectives include 1) mapping the epigenetic dynamics during infection in healthy subjects, 2) dissecting the mechanisms behind transmission of infection-triggered epigenetic changes, and 3) exploring the contribution of the epigenetic dynamics to infection severity and sequelae.

Our results will inform the development of tools for precision medicine as well as explain the fundamental mechanisms of infection-induced epigenetic rewiring.