Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
J Allergy Clin Immunol. 2015 Nov;136(5):1346-54.e1. doi: 10.1016/j.jaci.2015.01.042. Epub 2015 Mar 24.
Respiratory syncytial virus (RSV) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. Mast cells are important effector cells in allergy, with sentinel cell roles in host defense. However, the role of mast cells in response to RSV infection is unknown.
Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease.
Human cord blood-derived mast cells and the HMC-1 mast cell line were exposed to RSV or UV-inactivated RSV. Viral gene and protein expression were evaluated by using PCR and flow cytometry. The expression of interferon-stimulated genes and selected mediators were evaluated by using quantitative PCR and ELISA.
Human mast cells expressed multiple RSV genes after exposure to RSV, and a small percentage of mast cells supported RSV antigen protein expression. RSV induced mast cells to upregulate production of chemokines, including CCL4, CCL5, and CXCL10, as well as type I interferons, and interferon-stimulated gene expression. However, production of the granulocyte chemoattractants CXCL8 and CCL11 was not induced. Antibody blockade of the type I interferon receptor on human cord blood-derived mast cells reduced the RSV-mediated induction of CXCL10 and CCL4 but not CCL5. Leukotriene C4 production by mast cells was not enhanced by exposure to RSV.
Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease.
呼吸道合胞病毒（RSV）可引起严重的呼吸道感染，其可能在气道高反应性的发展中起作用。肥大细胞是过敏反应的重要效应细胞，在宿主防御中具有哨兵细胞的作用。然而，肥大细胞在 RSV 感染中的作用尚不清楚。
研究人肥大细胞对 RSV 的反应，以期更好地了解肥大细胞在 RSV 诱导疾病中的作用。
用 RSV 或 UV 灭活 RSV 处理人脐血来源的肥大细胞和 HMC-1 肥大细胞系。通过 PCR 和流式细胞术评估病毒基因和蛋白表达。通过定量 PCR 和 ELISA 评估干扰素刺激基因和选定介质的表达。
人肥大细胞在暴露于 RSV 后表达多个 RSV 基因，一小部分肥大细胞支持 RSV 抗原蛋白表达。RSV 诱导肥大细胞上调趋化因子的产生，包括 CCL4、CCL5 和 CXCL10，以及 I 型干扰素和干扰素刺激基因的表达。然而，并未诱导粒细胞趋化因子 CXCL8 和 CCL11 的产生。用针对 I 型干扰素受体的抗体阻断人脐血来源的肥大细胞可减少 RSV 介导的 CXCL10 和 CCL4 的诱导，但不能减少 CCL5。肥大细胞对 RSV 的暴露并未增强白细胞三烯 C4 的产生。
尽管感染水平较低，但人肥大细胞通过包括对 I 型干扰素的反应在内的机制对 RSV 产生多种趋化因子。这种肥大细胞反应可能会增强 RSV 诱导疾病期间效应细胞的募集。
