Role of Proinflammatory Fungal Lipoids in Fungal Inflammation

多态性白细胞代表宿主对真菌感染的先天免疫防御的主要成分，这表明真菌白细胞引诱剂和促炎细胞因子的参与。我们在各种真菌中发现了不稳定的脂质样白细胞化学引诱物，但在细菌或宿主细胞中没有。从酵母中纯化，结构分析和化学合成揭示了这些炎症介质作为一个新的脂质家族的成员，通过假定的G蛋白偶联受体激活中性粒细胞。该项目的目的是研究这些不稳定脂质在真菌炎症中的作用，特别是通过质谱法在不同病原真菌中鉴定这些脂质，并研究其产生条件。我们进一步观察到，酵母脂质提取物诱导角质形成细胞中的促炎细胞因子和趋化因子白细胞介素-8和RANTES。初步研究表明，这些脂质似乎至少部分在结构上不同于白细胞活化脂质。因此，它是进一步的目的，以阐明这些真菌类脂质的分子性质，并确定其假定的细胞受体。这些真菌特异性脂质，其宿主细胞受体和可能参与其生物合成的酶可能是真菌感染的新型抗炎治疗的靶点。

Polymorphonuclear leukocytes represent primary components of the host's innate immune defenses against fungal infection suggesting involvement of fungal leukocyte attractants and proinflammatory cytokines. We found in various fungi, but not in bacteria or host cells, unstable lipid-like leukocyte chemoattractants. Purification from yeast, structural analyses and chemical synthesis revealed these inflammatory mediators as members of a novel familiy of lipoids, which activate neutrophils via putative, G-protein-coupled receptors. It is the aim of this project to investigate the role of these unstable lipids in fungal inflammation, in particular to identify these lipoids by mass spectrometry in different pathogenic fungi and to investigate conditions of its production. We further observed, that yeast lipid extracts induced proinflammatory cytokines and the chemokines Interleukin-8 and RANTES in keratinocytes. Preliminary investigations showed, that these lipoids appear at least in part to be structurally different from leukocyte-activating lipoids. Therefore it is a further aim to elucidate the molecular nature of these cytokine-inducing fungal lipoids and to identify its putative cellular receptors. These fungus-specific lipoids, its host cell receptors and possibly the enzymes involved in its biosynthesis may be targets for a novel anti-inflammatory therapy in fungal infection.