Immune evasion of the human pathogenic yeast Candida albicans

白色念珠菌是最常见的人类致病性酵母菌，可引起皮肤和粘膜念珠菌病。这种二型酵母菌会导致危及生命的全身感染，特别是在免疫功能低下和粒细胞减少的患者中。在感染过程中，念珠菌暴露于人体免疫系统，并受到补体系统的攻击，补体系统是先天免疫的早期作用部分。目前尚不清楚念珠菌如何控制和逃避补体激活。最初，在酵母的表面上报道了宿主样补体受体CR2和CR 3（CD 11b/CD 18）的存在，然而迄今为止这些分子中没有一个在分子方面被鉴定。最近，宿主免疫调节剂和补体抑制剂因子H、FHL-1和C4 BP与念珠菌表面的连接已被证明介导补体和免疫逃避。在拟议的项目中，我们希望在分子水平上描述所连接的免疫调节剂的作用，并定义念珠菌存活和免疫逃逸的细胞和免疫学后果。克隆介导宿主调节因子在念珠菌表面粘附的分子，并分析选择性粘附的宿主免疫调节因子在宿主酵母相互作用中的作用，将描述一种新的念珠菌免疫逃避机制。这种方法有望鉴定新的毒力因子，从而确定致病酵母的药物开发新靶点。

Candida albicans is the most common human pathogenic yeast and causes cutanous and mucocutanous candidiasis. This dimorphic yeast causes life threatening systemic infections especially in immunocompromised and granulocytopenic patients. During infection candida is exposed to the human immune systems and is attacked by the complement system, which represents the early acting part of innate immunity. It is currently unclear how candida controls and evades complement activation. Initially the presence of host like complement receptors CR2 and CR3 (CD11b/CD18) were reported on the surface of the yeast, however none of these molecules has been identified in molecular terms so far. Recently, attachment of host immune regulators and complement inhibitors Factor H, FHL-1 and C4BP to the surface of candida have been shown to mediate complement and immune evasion. In the proposed project we want to characterize the role of the attached immune regulators in molecular terms and define the cellular and immunological consequences for survival and immune escape of candida. Cloning of the molecules which mediate attachment of host regulators on the candida surface and analyzing the role of the selectively attached host immune regulators for host yeast interaction will describe a novel immune evasion mechanism of candida. This approach is expected to identify new virulence factor(s) and thus define novel targets of the pathogenic yeast for drug development.