Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma
Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma
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DOI：
10.1038/nm.2896
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发表时间：
2012-10-01
期刊：
影响因子：
82.9
通讯作者：
Ray, Prabir
中科院分区：
文献类型：
--
作者：
Krishnamoorthy, Nandini;Khare, Anupriya;Ray, Prabir
免疫耐受在生命早期建立，在此期间调节性T（T-reg）细胞具有重要作用。呼吸道合胞病毒（RSV）在生命早期的反复感染会增加成年后患哮喘的风险。与未感染的耐受对照小鼠相比，通过其母乳用RSV重复感染对卵清蛋白（OVA）耐受的幼小鼠诱导过敏性气道疾病，以响应OVA致敏和激发，包括气道炎症、高反应性和较高的OVA特异性IgE。病毒感染诱导叉头盒P3（FOXP 3）（+）T-reg细胞中加塔-3表达和2型T辅助细胞（T（H）2）细胞因子产生，并以依赖于宿主中白细胞介素-4受体α（IL-4 R α）表达的方式损害肺T-reg细胞的抑制功能。因此，通过促进肺中的T（H）2型炎症反应，RSV在T-reg细胞中诱导T（H）2样效应子表型并减弱对无关抗原（过敏原）的耐受性。我们的研究结果强调了病毒感染在生命早期针对宿主保护机制并增加对过敏性疾病易感性的机制。
Immune tolerance is instituted early in life, during which time regulatory T (T-reg) cells have an important role. Recurrent infections with respiratory syncytial virus (RSV) in early life increase the risk for asthma in adult life. Repeated infection of infant mice tolerized to ovalbumin (OVA) through their mother's milk with RSV induced allergic airway disease in response to OVA sensitization and challenge, including airway inflammation, hyper-reactivity and higher OVA-specific IgE, as compared to uninfected tolerized control mice. Virus infection induced GATA-3 expression and T helper type 2 (T(H)2) cytokine production in forkhead box P3 (FOXP3)(+) T-reg cells and compromised the suppressive function of pulmonary T-reg cells in a manner that was dependent on interleukin-4 receptor alpha (IL-4R alpha) expression in the host. Thus, by promoting a T(H)2-type inflammatory response in the lung, RSV induced a T(H)2-like effector phenotype in T-reg cells and attenuated tolerance to an unrelated antigen (allergen). Our findings highlight a mechanism by which viral infection targets a host-protective mechanism in early life and increases susceptibility to allergic disease.