Effects of intranasal exposure to NKT cell ligand in neonatal respiratory syncytial virus infection on adult reinfection in mice

Abstract

Respiratory syncytial virus (RSV) is a major viral pathogen that causes severe lower respiratory tract infections in human infants worldwide. Infants with severe RSV bronchiolitis tend to experience more wheezing and asthma in later childhood. Because natural killer T (NKT) cells are associated with the pathology of asthma, we investigated whether neonatal NKT cells are involved in aggravation of pulmonary diseases following RSV infection. Intranasal exposure of the NKT cell ligand, ?-galactosylceramide (a-GC), with RSV primary infection in neonatal mice elicited neither cytokine production (except for a slight increase of IL-5) nor pulmonary eosinophilia despite of the presence of both CD1d+cells and NKT cells. Interestingly, in adult mice re-infected with RSV, neonatal NKT cell sensitization by a-GC during RSV primary infection resulted in much higher levels of pulmonary Th2 cytokines and elevated eosinophilia with severe airway hyperresponsiveness. In contrast, a-GC priming of adults during RSV re-infection did not induce more severe airway symptoms than RSV re-infection in the absence of a-GC. ?a-GC co-administration during RSV primary infection facilitates RSV clearance regardless of age, but the viral clearance following re-infection was not NKT cell-dependent. This study clearly demonstrates that RSV-induced immune responses can be altered by NKT cells, suggesting that neonatal NKT cell sensitization during RSV primary infection is strongly associated with exacerbation of pulmonary diseases following RSV re-infections in adulthood.