Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health. The University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Grafton Street, Manchester M13 9NT, UK.
Lydia Becker Institute of Immunology and Inflammation, Biology, Medicine and Health. The University of Manchester, Manchester Academic Health Science Centre.
FEMS Microbiol Rev. 2019 Mar 1;43(2):145-161. doi: 10.1093/femsre/fuy045.
Intracellular occupancy of the respiratory epithelium is a useful pathogenic strategy facilitating microbial replication and evasion of professional phagocytes or circulating antimicrobial drugs. A less appreciated but growing body of evidence indicates that the airway epithelium also plays a crucial role in host defence against inhaled pathogens, by promoting ingestion and quelling of microorganisms, processes that become subverted to favour pathogen activities and promote respiratory disease. To achieve a deeper understanding of beneficial and deleterious activities of respiratory epithelia during antimicrobial defence, we have comprehensively surveyed all current knowledge on airway epithelial uptake of bacterial and fungal pathogens. We find that microbial uptake by airway epithelial cells (AECs) is a common feature of respiratory host-microbe interactions whose stepwise execution, and impacts upon the host, vary by pathogen. Amidst the diversity of underlying mechanisms and disease outcomes, we identify four key infection scenarios and use best-characterised host-pathogen interactions as prototypical examples of each. The emergent view is one in which effi-ciency of AEC-mediated pathogen clearance correlates directly with severity of disease outcome, therefore highlighting an important unmet need to broaden our understanding of the antimicrobial properties of respiratory epithelia and associated drivers of pathogen entry and intracellular fate.
细胞内占据呼吸道上皮是一种有用的致病策略，有助于微生物的复制，并逃避专业吞噬细胞或循环中的抗菌药物。越来越多的证据表明，气道上皮在宿主抵御吸入性病原体方面也起着至关重要的作用，通过促进微生物的吞噬和抑制，这些过程被颠覆，有利于病原体的活动，并促进呼吸道疾病。为了更深入地了解呼吸道上皮在抗菌防御过程中的有益和有害活动，我们全面调查了所有关于气道上皮细胞摄取细菌和真菌病原体的现有知识。我们发现，气道上皮细胞（AECs）摄取微生物是呼吸道宿主-微生物相互作用的一个常见特征，其逐步执行及其对宿主的影响因病原体而异。在不同的潜在机制和疾病结果中，我们确定了四个关键的感染情况，并使用最具特征性的宿主-病原体相互作用作为每个情况的典型例子。出现的观点是，AEC 介导的病原体清除效率与疾病结果的严重程度直接相关，因此突出表明，需要扩大我们对呼吸道上皮的抗菌特性以及相关病原体进入和细胞内命运的驱动因素的理解，这是一个重要的未满足需求。
