Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
J Mol Biol. 2019 Jul 26;431(16):2982-3009. doi: 10.1016/j.jmb.2019.05.003. Epub 2019 May 9.
Environmental fungi are globally ubiquitous and human exposure is near universal. However, relatively few fungal species are capable of infecting humans, and among fungi, few exposure events lead to severe systemic infections. Systemic infections have mortality rates of up to 90%, cost the US healthcare system $7.2 billion annually, and are typically associated with immunocompromised patients. Despite this reputation, exposure to environmental fungi results in a range of outcomes, from asymptomatic latent infections to severe systemic infection. Here we discuss different exposure outcomes for five major fungal pathogens: Aspergillus, Blastomyces, Coccidioides, Cryptococcus, and Histoplasma species. These fungi include a mold, a budding yeast, and thermal dimorphic fungi. All of these species must adapt to dramatically changing environments over the course of disease. These dynamic environments include the human lung, which is the first exposure site for these organisms. Fungi must defend themselves against host immune cells while germinating and growing, which risks further exposing microbe-associated molecular patterns to the host. We discuss immune evasion strategies during early infection, from disruption of host immune cells to major changes in fungal cell morphology.
环境真菌在全球范围内无处不在,人类几乎普遍接触。然而,只有少数真菌物种能够感染人类,而在真菌中,只有少数暴露事件会导致严重的系统性感染。系统性感染的死亡率高达 90%,每年给美国医疗保健系统造成 72 亿美元的损失,而且通常与免疫功能低下的患者有关。尽管如此,接触环境真菌会导致一系列后果,从无症状的潜伏感染到严重的系统性感染。在这里,我们讨论了五种主要真菌病原体(曲霉菌、芽生菌、球孢子菌、隐球菌和组织胞浆菌)的不同暴露后果。这些真菌包括一种霉菌、一种出芽酵母和一种热双相真菌。所有这些物种都必须在疾病过程中适应急剧变化的环境。这些动态环境包括人类肺部,这是这些生物体的第一个暴露部位。真菌必须在发芽和生长的同时抵御宿主免疫细胞,这冒着将更多的微生物相关分子模式暴露给宿主的风险。我们讨论了早期感染期间的免疫逃避策略,从破坏宿主免疫细胞到真菌细胞形态的重大变化。