Signals derived from intestinal microbial communities augment anti-viral immunity (46.11)

Abstract

Abstract Alterations in intestinal microbial communities in humans are associated with enhanced susceptibility to inflammatory diseases suggesting that signals derived from commensal bacteria may influence the development and/or function of the immune system. Supporting this, germ-free (GF) mice exhibit reduced numbers of lymphocytes in the periphery and intestinal intraepithelial compartment. However, whether alterations in the composition of commensal bacteria influence immunity to infection remains poorly defined. To test this, mice housed under conventional (CNV) or GF conditions were infected with acute LCMV and the development of antigen-specific CD8+ T cell responses were analyzed. At day 7 p.i., GF mice exhibited a significant reduction in the frequency and number of LCMV-specific CD8+ T cells in multiple tissues including the spleen and intestinal intraepithelial compartment. The diminished CD8+ T cell response was not the result of inherent developmental defects in GF mice as depletion of intestinal bacteria in CNV mice via antibiotics also resulted in diminished LCMV-specific CD8+ T cell responses and impaired viral clearance. Further, adoptive transfer of CFSE-labeled LCMV-specific CD8+ T cells revealed a delay in the activation and expansion of LCMV-specific CD8+ T cells in antibiotic-treated mice. Collectively, these studies indicate that signals derived from intestinal bacteria aid in the induction of a rapid immune response required for immunity to viral infection.