The intestine, being home to more microbes then there are stars in our galaxy, represents a unique environment where our immune system, epithelial lining and the microbes co-exist in symbiotic harmony. But the tolerance of our immune system towards beneficial organisms does come with a high cost, as many viruses, such as HIV, have evolved to use this as a window of opportunity. By the time breach by harmful microbes is recognized by the immune system, it is often too late as the microbe has passed the portal of infection and the immune system may lose the race. In this project we aim to decipher the cellular mechanics of intestinal viral infections, factors that allow for their stealth invasion, and how specialized T cell mediated protective immunity is formed in the colon. By utilizing a novel model of LCMV rectal infection and various murine KO models, we are systematically studying the influence of different antigen presenting cells on CD8 T cell function and how tolerizing agents such as TGF-beta shape CD8 T cell responses as well as memory formation. Under ideal conditions a pathogen should be recognized and controlled at the site of entry however in the case of LCMV a delay in CD8 T cell response is the reason for a systemic spread of this RNA virus after rectal challenge. As we explore the virtually undescribed realms of colonic viral infections, we are beginning to understand the role of APC migration and their maturation for proper T cell priming, as well as how they function to contain overt immune activation. As timing and the quality of a robust CD8 T cell response is key, it remains paramount to identify the corresponding pattern recognition receptors and chemotactic strategies, not only to understand optimal T cell activation but also migration of effectors back to the site of infection and establishment of protective immunity. Ultimately, a better understanding of how protective immunity is established in the colon will inform the design of novel mucosal vaccination strategies.