The c-type lectin, Mincle, is a macrophage receptor for Candida albicans.

酵母菌白色念珠菌是一种重要的机会性感染，其在先天性或适应性免疫应答受损的患者中引起粘膜和播散性疾病。感染和增殖导致组织的真菌定殖，以及不同程度的组织损伤。后者是由生物体的毒力特性和宿主的基因组成决定的。这种大的细胞外病原体主要通过吞噬细胞从体内根除，吞噬细胞在确定相关组织病变的严重程度方面也很重要。巨噬细胞是先天性和适应性免疫反应的核心，它不仅能吸收并杀死酵母，而且能杀死并消化酵母，并将其成分呈递给适应性免疫系统的细胞。该项目基于以下假设：感染的结果和严重程度至少部分由巨噬细胞对酵母菌整体毒力特性的早期功能反应决定。这种反应是由与细胞表面受体的相互作用引发的，这项研究将表明，一种新型的巨噬细胞受体Mincle是真菌感染先天免疫反应的重要组成部分。我们已经证明，它与近交系小鼠对酵母菌感染的易感性差异有关;它可以区分不同的酵母菌分离株;它启动了炎症信号级联反应。我们的项目将确定该受体在真菌感染中的具体作用。这些结果对于理解宿主抗性的基础生物学将是重要的，并将通过选择性阻断或修饰不同的激活途径为治疗干预提供新的机会。

The yeast Candida albicans is an important opportunistic infection that causes both mucosal and disseminated disease in patients whose innate or adaptive immune responses are impaired Infection and proliferation results in fungal colonisation of the tissues, and a variable degree of tissue damage. The latter is determined both by the virulence properties of the organism and by the genetic makeup of the host. This large, extracellular pathogen is eradicated from the body predominantly by acavenger (phagocytic) cells, which are also important in determining the severity of the associated tissue lesions. A phagocytic cell that is central to both innate and adaptive immune responses is the macrophage, which not only takes up and kills the yeast, but also is capable of of killing and digesting it, and presenting the components to cells of the adaptive immune system. This project is based on the postulate that the outcome and severity of infection is determined, at least in part, by the early functional response of the macrophage to the overall virulence properties of the yeast. The response is initiated by interactions with cell-surface receptors, and this study will show that a novel macrophage receptor, Mincle, is an important part of the innate immune response to fungal infections. We have shown that it is associated with differences in susceptibility to yeast infections in inbred mouse strains; it can discriminate between different isolates of the yeast; and it initiates the inflammatory signalling cascade. Our project will define the specific role of this receptor in fungal infection. The results will be important in understanding the basic biology of host resistance, and will offer new opportunities for therapeutic intervention by selectively blocking or modifying different activation pathways.