| First Author | Durbin JE | Year | 2002 |
| Journal | J Immunol | Volume | 168 |
| Issue | 6 | Pages | 2944-52 |
| PubMed ID | 11884466 | Mgi Jnum | J:126678 |
| Mgi Id | MGI:3761867 | Doi | 10.4049/jimmunol.168.6.2944 |
| Citation | Durbin JE, et al. (2002) The role of IFN in respiratory syncytial virus pathogenesis. J Immunol 168(6):2944-52 |
| abstractText | Formalin-inactivated respiratory syncytial virus (RSV) vaccine preparations have been shown to cause enhanced disease in naive hosts following natural infection. In this study we demonstrate a similar pattern of enhanced disease severity following primary RSV infection of IFN-nonresponsive STAT1(-/-) mice. STAT1(-/-) mice showed markedly increased illness compared with wild-type BALB/c animals following RSV inoculation despite similar lung virus titers and rates of virus clearance. Histologically, STAT1(-/-) animals had eosinophilic and neutrophilic pulmonary infiltrates not present in wild-type or IFN-gamma(-/-)-infected mice. In cytokine analyses of infected lung tissue, IFN-gamma was induced in both STAT1(-/-) and wild-type mice, with preferential IL-4, IL-5, and IL-13 induction only in the STAT1(-/-) animals. Eotaxin was detected in the lungs of both wild-type and STAT1(-/-) mice following infection, with a 1.7-fold increase over wild-type in the STAT1(-/-) mice. Using a peptide epitope newly identified in the RSV fusion protein, we were able to demonstrate that wild-type memory CD4(+) T cells stimulated by this peptide produce primarily IFN-gamma, while STAT1(-/-)CD4(+) cells produce primarily IL-13. These findings suggest that STAT1 activation by both type I (alphabeta) and type II (gamma) IFNs plays an important role in establishing a protective, Th1 Ag-specific immune response to RSV infection. |
