病原真菌感染与TOLL样受体

TOLL样受体(TLR)是参与天然免疫的主要模式识别受体之一,与许多微生物病原体及其产物的病原相关分子模式PAMP结合后通过MyD88依赖性或非依赖性途径启动宿主胞内信号传导途径,引发一系列生物学效应。白色念珠菌表面的特征性糖磷脂甘露聚糖可被TLR2、TLR4识别,诱导前炎性细胞因子的释放及促进中性粒细胞的聚集等来介导宿主的抗真菌免疫反应。烟曲霉则可能利用表型转换(酵母样与菌丝态),通过不同TLRs逃避宿主天然免疫系统的识别。新型隐球菌的多糖荚膜成分葡糖醛氧化甘露聚糖GXM可与TLR2、TLR4、CD14结合,在单核细胞、巨噬细胞对GXM的内化、吞噬中起重要作用,而不是诱导细胞因子的分泌;酿酒酵母胞壁成分酵母多糖则可激活TLR2、TLR6异源二聚体。总之,TLR与真菌配体相互作用的具体机制及其活化后胞内信号传导调控机制的深入研究与分析,对临床真菌病的免疫调节及治疗具有重要意义。

Infection of Pathogenic Fungi and Toll-like Receptors

Toll-like receptors as the main partten recognition receptor involved in innate immunity can respond to the PAMPs of many microorganisms.After binding with its agonists, TLRs can trigger the intracellular signaling transduction and induce a series of physiological processes in MyD88-dependent or -independent way.PAMPs on the cell surface of common fungal pathogens are diverse, such as glucan, mannoproteins, the binding of fungal PAMPs to TLRs and TLRs-mediated regulation of immunological defence and tolerance of each fungi are distinct as well.The unique glycolipid present in the cell surface of Candida albicans phospholipomannan can be recognized by TLR2, TLR4, which induced the release of proinflammatory cytokines and promoted the recruitment of neutrophil cells.The major capsular polysaccharide of Cryptococcus neoformans was able to bind TLR2, TLR4 and CD14, which might have a crucial role in mediating the cellular internalization and phagocytosis by monocytes and neutrophis, instead of inducing secretion of cyto-kines.Aspergillus fumigatus may escape the recognition of innate immunity by taking advantage of phenotypic swithching (yeast and hypae) through TLRs.Yeast zymosan, a cell wall component of Saccharomyces cerevisiae, has been shown to activate heterodimers consisting of TLR2 and TLR6.In sum mary, further studies on the interaction between TLRs and its fungal ligands as well as the regulation of intracellular signaling transduction will contribute significantly to our understanding of immunoregulation of fungicidal disease, eventually provide some way to cure the fungal infection.