Antibiotic use in early life subsequently impairs MAIT cell-mediated immunity 2867

Abstract Description Although an association between antibiotic use in early life and increased susceptibility to infection has been described, the mechanisms behind this remain unclear. The development of mucosal associated invariant T (MAIT) cells is dependent on the recognition of derivatives of riboflavin produced by microbes during early-life. Therefore, we hypothesized that use of antibiotics during this period would deplete microbes that synthesize these metabolites and disrupt MAIT cell development and related immunity to infections. In vitro screening of antibiotics that are frequently prescribed to neonates was used to identify inhibitors of riboflavin-synthesizing commensals. Administration of these antibiotics to mice revealed a window when MAIT cell development is most affected by the depletion of riboflavin-synthesizing microbes. Antibiotic treatment of mice during this period resulted in a long-lasting reduction in MAIT cell abundance and an increased susceptibility to pneumonia, like what was observed in MAIT cell-deficient Mr1−/− mice, indicating the adverse impact on immunity is mediated by MAIT cells. Impaired MAIT cell development and immune response to pneumonia was rescued by concomitant delivery of a riboflavin-synthesizing bacteria during antibiotic treatment in early-life. Our work establishes a mechanism by which temporary disruption of the developing microbiome affects immune responses to infections later in life, highlighting the need for the development of probiotics. Funding Sources This work was supported by NIH K22AI146217; NIH R35GM151347 to M.G.C. and the NSF Graduate Research Fellowship to G.L. Topic Categories Mucosal and Regional Immunology (MUC)