Mincle is a novel macrophage receptor
Macrophages are critical effectors of innate immune responses to acute infections, and essential drivers of acquired immune responses to infectious disease. The definition of novel macrophage receptors and their pathways is of great significance, not only in understanding the biology of a cell crucial to both innate and adaptive immune responses, but in the development and application of new therapies. This project defines the function of Mincle, a novel macrophage receptor, which we have implicated in host responses to C. albicans infections. Mincle (macrophage inducible c-type lectin, otherwise known as Clecsf9) is a type-II transmembrane C-type lectin receptor. It forms part of the antigen-presenting lectin-like receptor complex on Human Chromosome 12, and is highly conserved in mammals. Mincle is so named because it is strongly induced in response to several inflammatory stimuli including LPS and type I interferons; however, very little is known about Mincle's function in macrophage biology, or in innate immunity in general. In this study, we report that Mincle is implicated in a mouse model of susceptibility to candidasis. Mincle forms part of a syn-expression group with Tlr2 in the acute phase of a yeast infection, which distinguishes it from other c-type lectins previously implicated in the phagocytosis of Candida, such as Dectin or the Mannose Receptor. We have demonstrated the localisation of Mincle to the nascent phagocytic cup of macrophages exposed to Candida. Blocking Mincle-ligand interactions with a neutralising anti-Mincle Ab attenuated the production of Tumour Necrosis Factor (TNF-?) in response to Candida infection by up to 30%. These data demonstrate a novel role for Mincle in host responses to C. Albicans, and our preliminary data indicates a wider role for Mincle in macrophage biology and immune surveillance. This ability to modify acute innate immune responses through co-receptors such as Mincle offers great potential for exploitation as an effective natural method of defence against opportunistic infections.