PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production

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Science Translational Medicine  09 May 2018:
Vol. 10, Issue 440, eaao0052
DOI: 10.1126/scitranslmed.aao0052

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RSV gives innate immunity the runaround

Asthma can be exacerbated by pathogens such as respiratory syncytial virus (RSV); prostaglandin D2 (PGD2) is also important in asthma and is being investigated as a therapeutic target. Werder et al. used multiple models to examine how RSV infection may perturb immune responses and influence asthma pathogenesis. Samples from infants with bronchiolitis or primary pediatric epithelial cells infected with RSV had elevated PGD2. Modulating PGD2 signaling in a mouse model of severe bronchiolitis improved antiviral immunity and dampened asthmatic symptoms later in life. This protection was not due to preventing type 2 immunity but instead a restoration of IFN-λ production. Their findings shed light on this host-pathogen interaction and suggest new therapeutic avenues.