The C-type lectin receptor mincle is functionally expressed by murine bone cells and can mediate inflammatory osteoblast responses to Staphylococcus aureus

It is now apparent that osteoblasts and osteoclasts have immune functions that play a critical role in shaping host responses and the abnormal bone remodeling associated with staphylococcal infections. Both cell types express various pattern recognition receptors (PRRs) that enable them to perceive pathogens and initiate the production of mediators that can exacerbate infection-induced inflammatory bone loss. Macrophage-inducible C-type lectin (Mincle) is a tyrosine activation motif–coupled PRR that can recognize glycolipids from diverse pathogens to initiate inflammatory mediator production. In the lung, an important role for Mincle has been suggested in host defense against Gram positive bacteria. In the present study, we report that RNA Tag-Seq analysis of S. aureus infected murine osteoclasts and osteoblasts revealed enrichment of genes associated with C-type lectin receptor-mediated responses and elevated expression of mRNA encoding Mincle and its key downstream signaling components. We have found robust levels of Mincle protein in murine osteoclasts and osteoblasts, and demonstrated the inducible expression of this molecule in primary human osteoblasts. The functional nature of Mincle expression by osteoclasts and osteoblasts was confirmed by the ability of Mincle-specific agonists to elicit inflammatory cytokine production by these cells. Importantly, we have showed that the cytokine responses of S. aureus challenged murine and human osteoblasts are attenuated following Mincle blockade. Together, these studies support the assertion that bone cells functionally express Mincle and that this C-type lectin can mediate, at least in part, the inflammatory immune responses of osteoblasts to S. aureus challenge. • Primary murine osteoclasts and osteoblasts express the C-type lectin receptor Mincle. • Mincle protein expression is inducible in primary human osteoblasts. • Mincle can mediate inflammatory cytokine production by osteoblasts and osteoclasts. • Osteoblast cytokine responses to Staphylococcus aureus are mediated in part by Mincle.