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

白念珠菌是一种重要的机会性感染，可引起黏膜和播散性疾病，其患者的固有免疫反应或获得性免疫反应受损，感染和增殖导致组织真菌定植，并造成不同程度的组织损伤。后者既由生物体的毒力特性决定，也由宿主的遗传组成决定。这种大型的细胞外病原体主要由吞噬细胞从体内根除，这些细胞在确定相关组织损伤的严重程度方面也很重要。巨噬细胞是先天免疫反应和获得性免疫反应的中心吞噬细胞，它不仅能吸收和杀死酵母菌，还能杀死和消化酵母，并将其成分提供给获得性免疫系统的细胞。这个项目是基于这样一个假设，即感染的结果和严重程度至少部分取决于巨噬细胞对酵母整体毒力特性的早期功能反应。这种反应是通过与细胞表面受体的相互作用而启动的，本研究将表明一种新的巨噬细胞受体Mincle是真菌感染的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感染的敏感性存在差异；它可以区分不同的酵母菌株；它还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。这一结果将对了解宿主耐药的基本生物学具有重要意义，并将为选择性地阻断或修改不同的激活途径而进行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.