Role for innate IFNs in determining respiratory syncytial virus immunopathology

Teresa R. Johnson, Sara E. Mertz, Negin Gitiban, Sue Hammond, Robin LeGallo, Russell K. Durbin, Joan E. Durbin

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Respiratory syncytial virus (RSV) is the major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. The difficulties involved in RSV vaccine development were recognized in an early vaccine trial, when children immunized with a formalin-inactivated virus preparation experienced enhanced illness after natural infection. Subsequent research in animal models has shown that the vaccine-enhanced disease is mediated at least in part by memory cells producing Th2 cytokines. Previously we had observed enhanced, eosinophilic lung pathology during primary infection of IFN-deficient STAT1-/- mice that are incapable of generating Th1 CD4+ cells. To determine whether these effects depended only on Th2 cytokine secretion or involved other aspects of IFN signaling, we infected a series of 129SvEv knockout mice lacking the IFN-αβR (IFN-αβR-/-), the IFN-γR (IFN-γR-/-), or both receptors (IFN-αβγR -/-). Although both the IFN-γR-/- and the IFN-αβγR-/- animals generated strong Th2 responses to RSV-F protein epitopes, predominantly eosinophilic lung disease was limited to mice lacking both IFNRs. Although the absolute numbers of eosinophils in BAL fluids were similar between the strains, very few CD8+ T cells could be detected in lungs of IFN-αβγR-/- animals, leaving eosinophils as the predominant leukocyte. Thus, although CD4+ Th2 cell differentiation is necessary for the development of allergic-type inflammation after infection and appears to be unaffected by type I IFNs, innate IFNs clearly have an important role in determining the nature and severity of RSV disease.

Original languageEnglish (US)
Pages (from-to)7234-7241
Number of pages8
JournalJournal of Immunology
Issue number11
StatePublished - Jun 1 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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