Respiratory Syncytial Virus Vaccine-Enhanced Pulmonary Eosinophilia Requires IL-13, IL-4Rα, and STAT6 (96.6)

Abstract

Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in children. A formalin-inactivated RSV vaccine administered to children in the 1960′s led to enhanced morbidity and mortality upon natural RSV infection. Histological analysis of the lungs upon autopsy revealed pulmonary eosinophilia. BALB/c mice primed with a recombinant vaccinia virus expressing the attachment (G) protein of RSV (vacG) develop pulmonary eosinophilia and vaccine-enhanced disease mimicking the response of the vaccinated children. Although the G protein elicits a mixed Th1 and Th2 response in these mice, the Th2 cells are known to be necessary for the induction of pulmonary eosinophilia. Here we have investigated role of individual Th2 cytokines in mediating RSV vaccine-enhanced disease. Our work shows that IL-13, the IL-4 receptor α chain (IL-4Rα), and STAT6, are required for the development of pulmonary eosinophilia in vacG-primed mice challenged with RSV whereas IL-4 is not required. We have found that IL-4, IL-13, IL-4Rα, and STAT6 do not contribute to weight loss or clinical illness whereas STAT4 is necessary. Lung histology and viral titers have also been examined in IL-13-, IL-4-, IL-4/13-, and IL-4Rα-deficient mice. Our results demonstrate a critical role for IL-13 in driving RSV vaccine-induced pulmonary eosinophilia.