Durbin, J EJ EDurbinFernandez-Sesma, AAFernandez-SesmaCHIEN-KUO LEERao, T DT DRaoFrey, A BA BFreyMoran, T MT MMoranVukmanovic, SSVukmanovicGarcía-Sastre, AAGarcía-SastreLevy, D ED ELevy2019-07-182019-07-182000-04-150022-1767https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034655279&doi=10.4049%2fjimmunol.164.8.4220&partnerID=40&md5=8b5a673d3929d4c8fc48ec22c9e9e0f9https://scholars.lib.ntu.edu.tw/handle/123456789/414251IFNs protect from virus infection by inducing an antiviral state and by modulating the immune response. Using mice deficient in multiple aspects of IFN signaling, we found that type I and type II IFN play distinct although complementing roles in the resolution of influenza viral disease. Both types of IFN influenced the profile of cytokines produced by T lymphocytes, with a significant bias toward Th2 differentiation occurring in the absence of responsiveness to either IFN. However, although a Th1 bias produced through inhibition of Th2 differentiation by IFN-gamma was not required to resolve infection, loss of type I IFN responsiveness led to exacerbated disease pathology characterized by granulocytic pulmonary inflammatory infiltrates. Responsiveness to type I IFN did not influence the generation of virus-specific cytotoxic lymphocytes or the rate of viral clearance, but induction of IL-10 and IL-15 in infected lungs through a type I IFN-dependent pathway correlated with a protective response to virus. Combined loss of both IFN pathways led to a severely polarized proinflammatory immune response and exacerbated disease. These results reveal an unexpected role for type I IFN in coordinating the host response to viral infection and controlling inflammation in the absence of a direct effect on virus replication.enjournal article10.4049/jimmunol.164.8.4220107543182-s2.0-0034655279https://api.elsevier.com/content/abstract/scopus_id/0034655279