Role for Innate IFNs in Determining Respiratory Syncytial Virus Immunopathology

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