Type I IFN modulates innate and specific antiviral immunity

Joan E. Durbin, Ana Fernandez-Sesma, Chien Kuo Lee, T. Dharma Rao, Alan B. Frey, Thomas M. Moran, Stanislav Vukmanovic, Adolfo García-Sastre, David E. Levy

Research output: Contribution to journalArticlepeer-review

238 Scopus citations


IFNs 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 vital 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-γ 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 vital 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 vital infection and controlling inflammation in the absence of a direct effect on virus replication.

Original languageEnglish
Pages (from-to)4220-4228
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - 15 Apr 2000


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