Toyotome Takahito, Watanabe Akira, Iwasaki Aya, Kamei Katsuhiko
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, Chiba, Japan.
Nihon Ishinkin Gakkai Zasshi. 2009;50(3):139-45. doi: 10.3314/jjmm.50.139.
Humans are continually inhaling environmental fungi. When the host immune system is competent, the inhaled fungi are cleared away from the lung by host defense mechanisms. But in immunocompromised individuals, the environmental fungi (e.g., Aspergillus fumigatus) sometimes cause infection. Pathogenic fungi possess various mechanisms to invade the host. A. fumigatus is no exception in possessing several virulence factors and defense mechanisms against host immune attack.One of the virulence factors is secondary metabolite. A. fumigatus produces a variety of secondary metabolites, and the fungal products in culture supernatant have a strong apoptosis-inducing activity to macrophages and alveolar epithelial cells. These data suggest that A. fumigatus is equipped with special projectile weapons for destroying host physical barriers and immunological barriers in lung.The fungal cell wall is an easy target for the host to recognize the pathogen. One of the fungal cell wall components, beta- (1,3) -glucan, is a major fungal PAMP (pathogen-associated molecular pattern), which is recognized by one of the pattern recognition receptors, dectin-1. The interaction induces activation of transcription factors and production of proinflammatory cytokines in the host cell. However, beta-glucan of A. fumigatus is strongly exposed to the surface only during the "swollen-conidia" phase. In the hyphal phase, the fungus is covered with "armor", i.e., other cell wall components to minimize the exposure of the beta-glucan structure. These findings suggest that A. fumigatus evades the recognition and the attack from host by masking beta-glucan. A. fumigatus has clever mechanisms to defend itself and to attack the host immune system.
人类持续吸入环境中的真菌。当宿主免疫系统功能正常时，吸入的真菌会被宿主防御机制从肺部清除。但在免疫功能低下的个体中，环境真菌（如烟曲霉）有时会引发感染。致病真菌拥有多种入侵宿主的机制。烟曲霉也不例外，它具有多种毒力因子以及抵御宿主免疫攻击的防御机制。其中一种毒力因子是次生代谢产物。烟曲霉会产生多种次生代谢产物，培养上清液中的真菌产物对巨噬细胞和肺泡上皮细胞具有很强的凋亡诱导活性。这些数据表明，烟曲霉配备了特殊的投射武器来破坏肺部的宿主物理屏障和免疫屏障。真菌细胞壁是宿主识别病原体的一个容易的靶点。真菌细胞壁的成分之一，β-(1,3)-葡聚糖，是一种主要的真菌病原体相关分子模式（PAMP），可被一种模式识别受体——dectin-1识别。这种相互作用会诱导宿主细胞中转录因子的激活和促炎细胞因子的产生。然而，烟曲霉的β-葡聚糖仅在“肿胀分生孢子”阶段强烈暴露于表面。在菌丝阶段，真菌被“盔甲”覆盖，即其他细胞壁成分，以尽量减少β-葡聚糖结构的暴露。这些发现表明，烟曲霉通过掩盖β-葡聚糖来逃避宿主的识别和攻击。烟曲霉有巧妙的机制来保护自己并攻击宿主免疫系统。
