Laucirica Daniel R, Stick Stephen M, Garratt Luke W, Kicic Anthony
Wal-yan Respiratory Research Centre, Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.
Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, Australia.
Front Med (Lausanne). 2022 Dec 14;9:1069929. doi: 10.3389/fmed.2022.1069929. eCollection 2022.
Persistent respiratory bacterial infections are a clinical burden in several chronic inflammatory airway diseases and are often associated with neutrophil infiltration into the lungs. Following recruitment, dysregulated neutrophil effector functions such as increased granule release and formation of neutrophil extracellular traps (NETs) result in damage to airway tissue, contributing to the progression of lung disease. Bacterial pathogens are a major driver of airway neutrophilic inflammation, but traditional management of infections with antibiotic therapy is becoming less effective as rates of antimicrobial resistance rise. Bacteriophages (phages) are now frequently identified as antimicrobial alternatives for antimicrobial resistant (AMR) airway infections. Despite growing recognition of their bactericidal function, less is known about how phages influence activity of neutrophils recruited to sites of bacterial infection in the lungs. In this review, we summarize current and findings on the effects of phage therapy on neutrophils and their inflammatory mediators, as well as mechanisms of phage-neutrophil interactions. Understanding these effects provides further validation of their safe use in humans, but also identifies phages as a targeted neutrophil-modulating therapeutic for inflammatory airway conditions.
持续性呼吸道细菌感染是几种慢性炎症性气道疾病的临床负担，通常与中性粒细胞浸润肺部有关。在募集后，中性粒细胞效应功能失调，如颗粒释放增加和中性粒细胞胞外陷阱（NETs）形成，会导致气道组织损伤，促进肺部疾病进展。细菌病原体是气道嗜中性粒细胞炎症的主要驱动因素，但随着抗菌药物耐药率上升，传统的抗生素治疗感染的方法正变得越来越无效。噬菌体现在经常被确定为抗微生物耐药（AMR）气道感染的抗菌替代品。尽管人们越来越认识到它们的杀菌功能，但对于噬菌体如何影响募集到肺部细菌感染部位的中性粒细胞活性却知之甚少。在这篇综述中，我们总结了目前关于噬菌体疗法对中性粒细胞及其炎症介质影响的研究结果，以及噬菌体与中性粒细胞相互作用的机制。了解这些影响不仅进一步验证了它们在人类中的安全使用，还将噬菌体确定为一种针对炎症性气道疾病的中性粒细胞调节疗法。
