Environmental Impact on Lifelong Immunity: The Role of Infection and Nutrition in Host Homeostasis

Abstract

The impact of environmental pressures on the immune system is significant and complex. External influences contribute to immune development, cause or impact diseases, and fundamentally alter responses to future stressors. Infection and diet are two of the most profound external modifiers of host physiology. They can fundamentally alter normal biological pathways and lead to disparate phenotypes even in the context of identical genotypes, as in monozygotic twins. This dissertation will detail work that has investigated impacts of (i) lifelong infection and (ii) nutritional modulation upon host immunity, health, and lifespan. The first topic was addressed by studying the consequences of lifelong cytomegalovirus infection in the context of adipose tissue inflammation, viral persistence, and hyperglycemia. For the second, caloric restriction was used as a dietary intervention in old age and the consequences on immune cell populations across a spectrum of host tissues were studied. Obtained findings cross with the fields of immunology, gerontology, nutritional sciences, aging, virology, and endocrinology and have potentially significant and broad reaching consequences for human health.