Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma
Immune tolerance is instituted early in life, during which time regulatory T (Treg) 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 tolerised to ovalbumin (OVA) through their mother's milk with RSV induced allergic airway disease in response to OVA sensitisation and challenge, including airway inflammation, hyper-reactivity and higher OVA-specific IgE, as compared to uninfected tolerised control mice. Virus infection induced GATA-3 expression and T helper type 2 (TH2) cytokine production in forkhead box P3 (FOXP3)+ Treg cells and compromised the suppressive function of pulmonary Treg cells in a manner that was dependent on interleukin-4 receptor α (IL-4Rα) expression in the host. Thus, by promoting a TH2-type inflammatory response in the lung, RSV induced a TH2-like effector phenotype in Treg 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.
Citation: Nat Med. 2012 Oct;18(10):1525-30. doi: 10.1038/nm.2896. Epub 2012 Sep 9.
Publication Type: Journal article
Publisher: Nature Medicine