NKT cell-dependent differential effects of OPN on functional modulation of macrophages and T lymphocytes in RSV infection (HYP6P.273)

RSV bronchiolitis is an important cause of pediatric hospitalization, which often leads to developing asthma in later life. Studies have indicated a Th2 skewed polarization of the lung environment in these children, which can be modulated by exogenous administration of osteopontin (OPN). In this study, using an NKT cell KO (CD1d-/-) mouse model, we have examined the effects of OPN on macrophages (MQ) and T lymphocytes (Tc) during RSV infection and identified the role of NKT cells in this process. Flowcytometry analysis determined that OPN treatment in RSV infection had reduced MQ and Tc recruitment in the lung parenchyma and alveolar spaces. However, OPN induced activation of the CD4 and CD8 Tcs in an NKT- dependent fashion, as the magnitude of activation was reduced to only 20% in the CD1d-/- mice as compared to the wild type (WT) mice. Also, expression of MHCII on MQs was significantly increased in the CD1d-/- mice, indicating a downregulatory effect of NKT cells. Altogether, these data suggest that OPN differentially affects MQ and Tc response and their functional modulations in an NKT cell-dependent fashion. A better understanding of these inverse effects of OPN on different immune effector cells during RSV infection may help establish OPN as a potential therapeutic for prevention of RSV-associated asthma in children.