单核细胞抗烟曲霉感染作用的研究进展

Research progress on anti-Aspergillus fumigatus infection by monocytes

烟曲霉是临床常见的机会性致病真菌,好发于免疫低下人群,常因吸入孢子导致肺部感染,治疗困难。烟曲霉的致病性与其较强的生存能力有关,但主要取决于宿主免疫状态,尤其是天然免疫功能。单核细胞是天然免疫的重要效应细胞,可分化为树突细胞和巨噬细胞。依据其表面分子分型,单核细胞功能上分别以吞噬抗原、呈递抗原和杀伤抗原为特点,在抗烟曲霉感染中具有较高的抵御能力和诊断价值。现阶段研究基于不断发展的荧光标记、灌流培养、光谱成像、基因敲除等技术,通过体外细胞实验和小鼠体内实验,观察到单核细胞与烟曲霉相互作用。在烟曲霉孢子入侵早期,单核细胞即启动基因表达,直接杀灭孢子,也可通过增强中性粒细胞杀孢子活性间接参与抗感染免疫调节,其中白细胞介素家族可能是关键信号分子。

Aspergillus fumigatus (A. fumigatus) is an ubiquitous opportunistic fungus, which could cause serious pulmonary infection through inhalation of conidia. The infection is difficult to treat, and severity is strongly related to host immune status, especially innate immune functions. Monocytes are important effector cells in innate immune, which could be differentiated into dendritic cells and macrophages. Three subsets of monocytes defined by specific surface molecules exert distinguished functions in phagocytosis, antigen-presentation and conidiacidal activity. Based on the continuous development of assays, such as fluorescent tag, perfusion culture, spectral imaging, gene knockout technology, it is proven that monocytes play important roles in control of A. fumigatus infection in human and mouse. Monocytes could directly kill spores or improve neutrophil conidiacidal activity in the early A. fumigatus infection via interleukins signaling molecules.