MAIT cells protect against fatal pulmonary infection by Legionella species via IFNg and can be augmented by synthetic ligands. (#81)
Mucosal Associated Invariant T (MAIT) cells are an abundant subset of immune cells. MAIT cells are found to recognize metabolites derived from bacterial riboflavin synthesis presented by MHC-related 1 (MR1) molecule, which suggests that they play a critical role in immunity against bacterial infections. By using a murine pulmonary infection model with Legionella longbeachae, we found MAIT cells accumulated robustly at the site of infection and produced several critical cytokines to control the infection, including IFN-g, GM-CSF and IL-17A. We were able to show for the first time with a clinically relevant human pathogen that MAIT cells contributed to bacterial clearance in wild type mice and this protection role became more apparent in the absence of CD4+ T cells. Notably, adoptively transferred MAIT cells provide Rag2GammaC knockout mice with full protection against lethal Legionella infection in an IFN-g dependent manner. These findings suggest that MAIT cells are important to control Legionella longbeachae; a finding of potentially wider relevance to other intracellular infections. |