Wellemans Vincent, Benhassou Hassan Ait, Fuselier Eloise, Bellesort Fabienne, Dury Sandra, Lebargy François, Dormoy Valérian, Fichel Caroline, Naour Richard Le, Gounni Abdelilah S, Lamkhioued Bouchaib
CHU Sainte-Justine, Montréal, Québec, Canada.
Laboratoire d'Immunologie et de Biotechnologie, EA7509-IRMAIC, Pôle-Santé, Université de Reims Champagne-Ardenne, Reims, France.
iScience. 2021 Nov 14;24(12):103433. doi: 10.1016/j.isci.2021.103433. eCollection 2021 Dec 17.
Respiratory syncytial virus () infection is the principal cause of severe lower respiratory tract disease and accounts for a significant risk for developing asthma later in life. Clinical studies have shown an increase in airway responsiveness and a concomitant Th response in the lungs of RSV-infected patients. These indications suggest that RSV may modulate aspects of the immune response to promote virus replication. Here, we show that CCR3 facilitates RSV infection of airway epithelial cells, an effect that was inhibited by eotaxin-1/CCL11 or upon CCR3 gene silencing. Mechanistically, cellular entry of RSV is mediated by binding of the viral G protein to CCR3 and selective chemotaxis of Th cells and eosinophils. In vivo, mice lacking CCR3 display a significant reduction in RSV infection, airway inflammation, and mucus production. Overall, RSV G protein-CCR3 interaction may participate in pulmonary infection and inflammation by enhancing eosinophils' recruitment and less potent antiviral Th cells.
呼吸道合胞病毒（RSV）感染是严重下呼吸道疾病的主要原因，并且是日后患哮喘的重大风险因素。临床研究表明，RSV感染患者的气道反应性增加，同时肺部出现Th反应。这些迹象表明，RSV可能调节免疫反应的某些方面以促进病毒复制。在此，我们表明CCR3促进气道上皮细胞的RSV感染，这一效应被嗜酸性粒细胞趋化因子-1/CCL11或CCR3基因沉默所抑制。从机制上讲，RSV的细胞进入是由病毒G蛋白与CCR3的结合以及Th细胞和嗜酸性粒细胞的选择性趋化作用介导的。在体内，缺乏CCR3的小鼠的RSV感染、气道炎症和黏液分泌显著减少。总体而言，RSV G蛋白与CCR3的相互作用可能通过增强嗜酸性粒细胞的募集和降低抗病毒Th细胞的活性来参与肺部感染和炎症。
