Regulation of early life immunity by maternal microchimeric cells

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PI/PD: Jain, Nitya Ph.D. PROJECT SUMMARY Early life immunity develops and matures over a period of time, leaving newborns susceptible to adverse microbial encounters. Indeed, bacterial infections are a major cause of mortality in preterm and term newborns. Protective maternal factors transferred to offspring are a crucial line of defense during this vulnerable period. One arm of this protection arises from engrafted maternal microchimeric cells (MMCs) that are transferred into the offspring during pregnancy. In humans, MMCs have the potential to alter offspring immune responses to antigenic challenge including malarial and Epstein-Barr virus infection. Whether maternal immune states arising from infection and immunization during pregnancy alters the nature of microchimerism and subsequent offspring immune responses is unknown. Our proposal addresses this knowledge gap. Accumulating evidence, most recently from the SARS-CoV-2 pandemic, indicate that many infectious diseases affect children differently than adults. Understanding these differences, including how maternal factors contribute to the functional plasticity of early life immune responses, will yield important insight into disease pathogenesis and inform development of new therapeutics.