Adhvaith Sridhar

Normalizing Microbial Exposure from the Earliest Natural Timepoint Enhances Neonatal Host Defense

Mus musculus (mice) are often used to model the human immune system and to develop healthcare treatments, vaccines, and drugs because mouse immunology accurately recapitulates many aspects of the human immune system. However, differences between the immunology of lab mice and the true human immune system may decrease the predictive power of treatments developed in mice. One limitation of using mouse models to study human immune conditions is the relative immune immaturity of laboratory mice. Immune maturity is a key component in any organism’s ability to resist disease and infection. This project aims to redefine treatments geared towards infant human immune systems by showing that preconception normalized microbial exposure (pNME) pups, which have undergone pNME from conception, have accelerated immune development relative to specific pathogen free counterparts and more accurately recapitulate human immune development than typical specific pathogen free (SPF) models. For this research, tissue samples from 120 mice were characterized. The hypothesis was supported, indicating that the use of SPF conditions for laboratory mice in preclinical and research studies leaves the immune systems of infant mice underdeveloped and far different from the immune systems found in human infants. The data presented herein further demonstrated that infant pNME mice develop elevated profiles of a variety of components during different stages in development and better reflect human infant immunity. Applying Listeria monocytogenes challenges to pNME mice demonstrated the physiological changes associated with the changed immune composition. This work is critical in advancing human health and accurately applying preclinical findings.