Departments of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Immunology. 2018 Oct;155(2):155-163. doi: 10.1111/imm.12953. Epub 2018 Jun 14.
The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged, often in the form of helper CD4 T-cell responses. Type 1 responses, characterized by interferon-γ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, interleukin-17A (IL-17A) production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidioides species infection by recruiting neutrophils. In contrast the development of T helper type 2 responses, characterized by IL-5 production from T cells and eosinophil influx into the lungs, drives allergic bronchopulmonary aspergillosis and poor outcomes during C. neoformans infection. Experimental vaccines against several endemic mycoses, including Histoplasma capsulatum, Coccidioides, Cryptococcus and Blastomyces dermatitidis, induce protective T-cell responses and foreshadow the development of vaccines against pulmonary fungal infections for use in humans. Additionally, recent work using antifungal T cells as immunotherapy to protect immune-compromised patients from opportunist fungal infections also shows great promise. This review covers the role of T-cell responses in driving protection and pathology in response to pulmonary fungal infections, and highlights promising therapeutic applications of antifungal T cells.
呼吸道的黏膜表面在每次呼吸时都会接触到微生物，如真菌颗粒。当致病性真菌突破肺部的物理屏障和先天免疫系统而引发感染时，适应性免疫就会被激活，通常表现为辅助性 CD4 T 细胞应答。以 CD4 细胞产生干扰素-γ为特征的 1 型应答促进荚膜组织胞浆菌和新生隐球菌感染的清除。同样，Th17 细胞产生的白细胞介素-17A（IL-17A）通过招募中性粒细胞促进皮炎芽生菌和粗球孢子菌感染的免疫。相比之下，T 辅助细胞 2 型反应的发展，其特征是 T 细胞产生 IL-5 和嗜酸性粒细胞涌入肺部，导致过敏性支气管肺曲霉病和新型隐球菌感染的不良结局。针对几种地方性真菌病（包括荚膜组织胞浆菌、粗球孢子菌、隐球菌和皮炎芽生菌）的实验性疫苗可诱导保护性 T 细胞应答，并预示着针对肺部真菌感染的疫苗的开发将用于人类。此外，最近使用抗真菌 T 细胞作为免疫疗法来保护免疫功能低下的患者免受机会性真菌感染的工作也显示出巨大的前景。这篇综述涵盖了 T 细胞应答在驱动肺部真菌感染的保护和发病机制中的作用，并强调了抗真菌 T 细胞有希望的治疗应用。
