Mouse model of neonatal fungal colonization to study homeostasis and disease

SUMMARY While the fungus Candida albicans has largely been studied as a pathogen, its primary lifestyle is as a commensal on mucosal surfaces, including the oral cavity. Microorganisms that occupy mucosal surfaces are critical for appropriately tuning immune responses to ensure efficient responses to invading pathogens while limiting responses directed towards host tissues. In this context, commensal fungi play important roles in host immunity and inflammation. For instance, C. albicans colonization induces cross-reactive T cells and innate memory in immune cells, a mechanism termed trained immunity. Accumulating evidence from our group and others have convincingly demonstrated that oral commensal colonization with C. albicans induces specific immune responses, therefore contributing to mucosal immune system plasticity. However, our knowledge of antifungal immunity is based on data of adult animals. Importantly, humans are colonized with C. albicans during birth. Furthermore, the neonatal immune system has long been regarded immature when compared to the adult immune system. However, is becomes clear that neonatal immunity is specifically adapted to prevent pathogen invasion, while supported its development. However, the fundamental immunological consequences of C. albicans colonization in neonates are still unknown. We developed a novel mouse model of commensal Candida colonization in neonates. This proposal will characterize oral mucosal immune cell populations in neonates in response to commensal Candida colonization (Aim 1) and elucidate age related differences in IL- 17 and IL-22 immunity during oral fungal colonization (Aim 2).