Antibiotic induced intestinal dysbiosis in infant mice impacts CD8+ T cell anti-viral immune function and control of infection (IRC8P.494)

Abstract

Abstract Infancy and childhood is a critical period for the development of long-term immune function. Normal acquisition of the gastrointestinal (GIT) flora during this period is now appreciated in its role on immune system development and function. Antibiotics cause GIT flora dysbiosis and may alter normal GIT colonization during infancy. Subsequently, immune development and function may also be affected. In this infant mouse model of antibiotic mediated GIT flora dysbiosis, perinatal antibiotic treatment (AT) alters the composition of the GIT flora in mothers and their infants. CD8+ T cells from AT infant mice activated in vitro with cytokines, proliferate, express activation markers, and produce IFN-γ. However, unlike non-antibiotic treated (CTRL) infant mice, AT mice succumb to vaccinia virus infection. AT infant mice survive sub-lethal infection indicating effective primary immune responses to control infection. Interestingly, the expansion of Teff, Tem, and Tcm subsets differs between CTRL and AT sub-lethally infected infant mice. Transfer of OT-I T cells into AT infant mice prior to lethal infection rescues these mice from death. However, expansion of OT-I T cells is limited in AT infant mice and the differential expression of effector and memory cell markers is also recapitulated. These results suggest that dysbiosis during infancy negatively impacts effective adaptive primary immune responses and has potential consequences on memory T cell development.