Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT, United States.
Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Front Immunol. 2020 Feb 11;11:91. doi: 10.3389/fimmu.2020.00091. eCollection 2020.
Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the lung, not only serving as building blocks but also providing immune protection throughout the lung. Epithelial cells function either independently to eradicate the pathogen or communicate with immune cells to orchestrate pathogen clearance. The epithelial cells have multiple mechanisms that include mucus production, antimicrobial peptide production, muco-ciliary clearance, and phagocytosis, all of which contribute to their direct antibacterial function. Secretion of cytokines to recruit immune cells and potentiate their antimicrobial activities is a pathway by which the epithelium contributes to bacterial clearance. Successful pathogens outsmart epithelial resistance and find a way to replicate in sufficient numbers to establish infections in the airway or lung epithelial surfaces. In this mini-review, we discuss evidences that establish important roles for epithelial host defense against invading respiratory bacterial pathogens and demonstrate how pathogens outsmart these epithelial immune mechanisms to successfully establish infection. Finally, we discuss briefly how to boost epithelial immunity to improve outcomes in bacterial lung infections.
细菌肺部感染是全球范围内导致数百万人死亡并造成巨大经济负担的主要医疗保健挑战。基础和临床研究都阐明了宿主机制,这些机制有助于清除细菌,其中免疫细胞的作用不可或缺。然而,由于与巨噬细胞和中性粒细胞等免疫细胞相比,呼吸道上皮细胞的炎症或吞噬能力较弱,因此其在清除细菌中的作用一直受到关注。这些研究往往忽略了一个事实,即上皮细胞是肺部最丰富的细胞,不仅是构建块,而且在整个肺部提供免疫保护。上皮细胞可以独立地消灭病原体,或者与免疫细胞进行交流以协调病原体的清除。上皮细胞有多种机制,包括粘液产生、抗菌肽产生、黏液纤毛清除和吞噬作用,所有这些都有助于其直接的抗菌功能。分泌细胞因子招募免疫细胞并增强其抗菌活性是上皮细胞有助于清除细菌的途径之一。成功的病原体能够智取上皮细胞的抵抗力,并找到一种方法在呼吸道或肺上皮表面大量复制以建立感染。在这篇综述中,我们讨论了证据,这些证据确立了上皮细胞在抵御入侵的呼吸道细菌病原体方面的重要作用,并展示了病原体如何智取这些上皮细胞免疫机制以成功建立感染。最后,我们简要讨论了如何增强上皮细胞免疫以改善细菌肺部感染的结果。