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Thus, GAS is also known as \u201ckiller bacteria\u201d or \u201cflesh-eating bacteria.\u201d The mechanism by which the immune system recognizes this potent pathogen remains elusive. In this study, we showed that the innate immune receptor Mincle (macrophage inducible C-type lectin) plays pivotal roles against invasive GAS infection through the recognition of monoglucosyldiacylglycerol (MGDG), a component of the lipoteichoic acid anchor. MGDG induced proinflammatory cytokines, ROS, and NO production in a Mincle-dependent manner. In an invasive GAS infection model, Mincle-deficient mice exhibited severe bacteremia and rapid lethality. 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