The Interaction of with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense against Infection.

pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels. Mouse macrophages overexpressing Mincle displayed increased binding to life forms and enhanced protein tyrosine phosphorylation. The binding of to Mincle resulted in activation of FcRγ-mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after challenge, critical in downstream inflammatory signaling. Mincle-deficient CD4-depleted (Mincle) mice showed a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during pneumonia. Interestingly, Mincle mice did not demonstrate worsened survival during PCP compared with wild-type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle mice. Of note, the -infected Mincle mice demonstrated increased expression of known C-type lectin receptors Dectin-1, Dectin-2, and MCL compared with infected wild-type mice. Taken together, these data support a significant role for Mincle in modulating host defense during infection.