Ectopic Expression of C-Type Lectin Mincle Renders Mice Susceptible to Staphylococcal Pneumonia.

Staphylococcus aureus is a prevalent pathogen in pneumonia and harbors glycolipids, which may serve as molecular patterns in Mincle (macrophage-inducible C-type lectin)–dependent pathogen recognition. We examined the role of Mincle in lung defense against S aureus in wild-type (WT), Mincle knockout (KO), and Mincle transgenic (tg) mice. Two glycolipids, glucosyl-diacylglycerol (Glc-DAG) and diglucosyl-diacylglycerol (Glc₂-DAG), were purified, of which only Glc-DAG triggered Mincle reporter cell activation and professional phagocyte responses. Proteomic profiling revealed that Glc₂-DAG blocked Glc-DAG–induced cytokine responses, thereby acting as inhibitor of Glc-DAG/Mincle signaling. WT mice responded to S aureus with a similar lung pathology as Mincle KO mice, most likely due to Glc₂-DAG–dependent inhibition of Glc-DAG/Mincle signaling. In contrast, ectopic Mincle expression caused severe lung pathology in S aureus –infected mice, characterized by bacterial outgrowth and fatal pneumonia. Collectively, Glc₂-DAG inhibits Glc-DAG/Mincle–dependent responses in WT mice, whereas sustained Mincle expression overrides Glc₂-DAG–mediated inhibitory effects, conferring increased host susceptibility to S aureus. [ABSTRACT FROM AUTHOR]