Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4
Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4
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DOI：
10.1016/j.jaci.2015.01.042
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发表时间：
2015-11-01
影响因子：
14.2
通讯作者：
Marshall, Jean S.
中科院分区：
文献类型：
--
作者：
Al-Afif, Ayham;Alyazidi, Raidan;Marshall, Jean S.
背景资料：呼吸道合胞病毒（RSV）引起严重的呼吸道感染，这可能在气道高反应性的发展中发挥作用。肥大细胞是变态反应中重要的效应细胞，在宿主防御中具有前哨细胞的作用。然而，肥大细胞在响应RSV infection.Objective的作用：人肥大细胞反应RSV进行了研究，以期更好地了解肥大细胞在RSV-induced diseases.Methods的作用：人脐血来源的肥大细胞和HMC-1肥大细胞系暴露于RSV或UV灭活的RSV。用PCR和流式细胞术检测病毒基因和蛋白表达。用定量PCR和ELISA方法检测干扰素刺激基因和选定介质的表达。结果：人肥大细胞暴露于RSV后表达多个RSV基因，少量肥大细胞支持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CCL 4、CCL 5和CXCL 10，以及I型干扰素和干扰素刺激的基因表达。然而，粒细胞趋化因子CXCL 8和CCL 11的产生没有被诱导。抗体阻断人脐带血来源的肥大细胞上的I型干扰素受体可降低RSV介导的CXCL 10和CCL 4诱导，但不降低CCL 5诱导。暴露于RSV.Conclusion：尽管低水平的感染，人肥大细胞产生多种趋化因子响应RSV通过机制，包括响应I型干扰素。这种肥大细胞反应可能会增强RSV诱导的疾病过程中效应细胞的募集。
Background: 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.Objective: Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease.Methods: 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.Results: 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.Conclusion: 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.