Calvert Ben A, Quiroz Erik J, Lorenzana Zareeb, Doan Ngan, Kim Seongjae, Senger Christiana N, Anders Jeffrey J, Wallace Wiliam D, Salomon Matthew P, Henley Jill, Ryan Amy L
Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States.
Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa, IA, United States.
Front Immunol. 2023 Mar 16;14:1112870. doi: 10.3389/fimmu.2023.1112870. eCollection 2023.
In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre- existing co-morbidities correlating to incidence to severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS-CoV-2 infection.
To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. This model was infected with live SARS-CoV-2 virus the epithelial response to infection was evaluated.
SARS-CoV-2 infection of airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented proinflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory responses are polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the \epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells.
This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity.
作为固有免疫反应的一部分，中性粒细胞在病毒感染时会释放炎症介质，通过病毒内化和杀伤作用促进病原体清除。与严重 COVID-19 发病率相关的既往合并症与慢性气道中性粒细胞增多有关。此外，对 COVID-19 外植肺组织的检查发现了一系列与中性粒细胞浸润和活化相关的上皮病变，表明中性粒细胞对 SARS-CoV-2 感染有反应。
为了确定中性粒细胞与上皮细胞相互作用对 SARS-CoV-2 感染的传染性和炎症反应的影响，我们建立了气道中性粒细胞增多的共培养模型。用活的 SARS-CoV-2 病毒感染该模型，并评估上皮细胞对感染的反应。
单独的气道上皮细胞感染 SARS-CoV-2 不会导致上皮细胞产生显著的促炎反应。添加中性粒细胞会诱导促炎细胞因子的释放，并在随后的 SARS-CoV-2 感染中刺激显著增强的促炎反应。由此产生的炎症反应呈极化状态，上皮细胞顶端和基底外侧释放的物质有所不同。此外，上皮屏障的完整性受损，出现明显的上皮损伤和基底干细胞感染。
本研究揭示了中性粒细胞与上皮细胞相互作用在决定炎症和传染性方面的关键作用。
