Characterization of mucosal-associated invariant T cell response during Acinetobacter baumannii infections 4736

Abstract Description Nosocomial infections with multidrug-resistant bacteria are an increasing public health concern. One example is Acinetobacter baumannii, a gram-negative bacterium capable of causing pneumonic, systemic, and dermal infections. A cell type primed to respond to A. baumannii is mucosal-associated invariant T (MAIT) cells. MAIT cells canonically respond to microbial riboflavin synthesis, allowing them to act as early responders to infection and bridge innate and adaptive immunity. Although MAIT cells have been shown to clear various bacterial pathogens, their role in A. baumannii infections has yet to be elucidated. Our work demonstrates that diverse A. baumannii strains activate MAIT cells utilizing an in vitro co-culture system. Murine lung infection models demonstrate that MAIT cells also expand in vivo. These expanded MAIT cells are tissue-localized, Th17-like cells with high IL-17A production upon ex vivo re-stimulation. To identify cell types promoting this MAIT cell response, we utilized Cre-lox mice to delete antigen-presenting molecules in specific cell subsets. These models indicate that MAIT cell response to A. baumannii is dependent on non-classical MHC class I molecule, MR1. We further demonstrate that a combination of hematopoietic and non-hematopoietic subsets present antigen during A. baumannii infections. This work identifies MAIT cells as a novel therapeutic target for A. baumannii and elucidates how these lymphocytes respond to this high-priority pathogen. Funding Sources This work was supported by the NIH (K22AI146217 & R35GM151347 to M.G.C.). Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)