Westmead Hospital, Westmead NSW, Australia.
Adv Exp Med Biol. 2009;666:108-20. doi: 10.1007/978-1-4419-1601-3_9.
Invasive fungal infections are an increasing clinical problem for which new therapeutic approaches are needed. Understanding the initial interaction between fungi and the host offers potential for development of new drugs or vaccines. It has recently been recognized that like other pathogens, fungi initially interact with the innate immune system via binding between fungus-specific chemical signatures (pattern-associated molecular patterns or PAMPs) and pattern recognition receptors (PRRs) on mononuclear phagocytes. Fungal PAMPs are restricted to complex carbohydrates in the cell wall, including mannoproteins, phospholipomannan, beta-glucans and possibly chitin. These PAMPs bind specifically to two classes of PRR in phagocyte membranes, toll-like receptors and C-lectin-like receptors, through which they initiate signaling responses that culminate in release of pro- and anti-inflammatory cytokines, link the innate immune response with the adaptive immune response and initiate phagocytosis and intracellular killing. Isolated PAMPs have been used to dissect phagocyte responses in vitro and have revealed mechanisms by which host cells can tailor innate immune responses to individual pathogens. The interactions are complex and are yet to be translated into a clear understanding of the roles of the respective PAMPs and PRRs in vivo. Recent advances in this area in relation to the pathogenesis of fungal infections are summarized in this chapter.
侵袭性真菌感染是一个日益严重的临床问题，需要新的治疗方法。了解真菌与宿主的初始相互作用为开发新的药物或疫苗提供了潜力。最近人们认识到，与其他病原体一样，真菌最初通过真菌特异性化学标记物（模式相关分子模式或 PAMPs）与单核吞噬细胞上的模式识别受体（PRRs）之间的结合与先天免疫系统相互作用。真菌 PAMPs 仅限于细胞壁中的复杂碳水化合物，包括甘露糖蛋白、磷壁酸、β-葡聚糖和可能的几丁质。这些 PAMPs 通过吞噬细胞膜中的两类 PRR（ Toll 样受体和 C-凝集素样受体）特异性结合，通过这些受体启动信号反应，最终导致促炎和抗炎细胞因子的释放，将先天免疫反应与适应性免疫反应联系起来，并启动吞噬作用和细胞内杀伤。已将分离的 PAMPs 用于体外剖析吞噬细胞反应，并揭示了宿主细胞如何针对个别病原体定制先天免疫反应的机制。这些相互作用很复杂，尚未转化为对体内各自 PAMPs 和 PRRs 作用的清晰理解。本章总结了该领域在真菌感染发病机制方面的最新进展。
