Institute for Hygiene and Microbiology, University of Würzburg, Germany; Septomics Research Center, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany.
Institute for Hygiene and Microbiology, University of Würzburg, Germany; Septomics Research Center, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany.
Semin Cell Dev Biol. 2019 May;89:3-15. doi: 10.1016/j.semcdb.2018.03.021. Epub 2018 Apr 7.
Fungal pathogens cause severe and life-threatening infections worldwide. The majority of invasive infections occurs in immunocompromised patients and is based on acquired as well as congenital defects of innate and adaptive immune responses. In many cases, these defects affect phagocyte functions. Consequently, professional phagocytes - mainly monocytes, macrophages, dendritic cells and polymorphonuclear neutrophilic granulocytes - have been shown to act as central players in initiating and modulating antifungal immune responses as well as elimination of fungal pathogens. In this review we will summarize our current understanding on the role of these professional phagocytes in invasive fungal infection to emphasize two important aspects. (i) Analyses on the interaction between fungi and phagocytes have contributed to significant new insights into phagocyte biology. Important examples for this include the identification of pattern recognition receptors for β-glucan, a major cell wall component of many fungal pathogens, as well as the identification of genetic polymorphisms that determine individual host responses towards invading fungi. (ii) At the same time it was shown that fungal pathogens have evolved sophisticated mechanisms to counteract the attack of professional phagocytes. These mechanisms range from complete mechanical destruction of phagocytes to exquisite adaptation of some fungi to the hostile intracellular environment, enabling them to grow and replicate inside professional phagocytes.
真菌病原体在全球范围内引起严重且危及生命的感染。大多数侵袭性感染发生在免疫功能低下的患者中,并且基于先天和适应性免疫反应的获得性和先天性缺陷。在许多情况下,这些缺陷会影响吞噬细胞的功能。因此,专业的吞噬细胞——主要是单核细胞、巨噬细胞、树突状细胞和多形核中性粒细胞——已被证明是启动和调节抗真菌免疫反应以及消除真菌病原体的核心参与者。在这篇综述中,我们将总结我们目前对这些专业吞噬细胞在侵袭性真菌感染中的作用的理解,以强调两个重要方面。(i) 对真菌与吞噬细胞相互作用的分析为吞噬细胞生物学提供了重要的新见解。这方面的重要例子包括识别β-葡聚糖的模式识别受体,β-葡聚糖是许多真菌病原体细胞壁的主要成分,以及确定个体宿主对入侵真菌反应的遗传多态性的鉴定。(ii) 同时表明,真菌病原体已经进化出复杂的机制来对抗专业吞噬细胞的攻击。这些机制范围从吞噬细胞的完全机械破坏到一些真菌对恶劣的细胞内环境的精细适应,使它们能够在专业吞噬细胞内生长和复制。