Characterizing the MAIT cell response to intracellular pulmonary infection 2704

Abstract Description Mucosal-associated invariant T (MAIT) cells are an effector population of innate-like T cells that comprise up to 5% of T cells within human lungs and have been shown to promote immunity against an array of pulmonary pathogens in vivo. Rather than recognizing peptides like conventional T cells, MAIT cells identify microbial metabolites and other small molecules presented by MHC-class 1 related protein (MR1). Because MR1 is expressed by many cell types, the antigen presentation cells (APCs) that display microbial metabolites to MAIT cells during bacterial infection remain unknown, preventing optimization of MAIT cell vaccines. Utilizing the F. tularensis live vaccine strain to induce pneumonic tularemia, we found that MAIT cells respond in an MR1 dependent manner to become the predominant effector T cell population. Preventing egress from secondary lymphoid organs indicated that MR1 presentation occurs both locally and within lymph nodes. Targeted depletion of APCs and deletion of MR1 using cell-specific Cre strains and an Mr1f/f conditional knockout allowed us to determine the relative contributions of dendritic cells, macrophages, and monocyte-derived cells. Preventing MR1-mediated presentation decreased survival to F. tularensis. This work identifieswhich APCs are critical for MAIT cell activation during an intracellular bacterial infection and identifies cellular targets to enhance MAIT cell responses. Funding Sources K22AI146217 & R35GM151347 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)