RSV-induced polarization of lung DCs towards plasmacytoid DCs with an associated Th2 response is dependent on NKT cells in the neonatal lungs (37.46)

Abstract

RSV bronchiolitis and pneumonia during early infancy is associated with increased susceptibility to asthma; and is characterized by a hyper-responsiveness airway and a predominant Th2 response. Using a BALB/C neonatal mouse model we have observed a skewed polarization of DCs towards plasmacytoid DCs (pDCs: CD11blo CD11clo CD45R+) over myeloid DC (mDCs: CD11blo CD11chi/med CD45R-), as determined by flow cytometry (FACS). This was associated with increased and decreased production of Th2 (IL-10) and Th1 (IFN-g) cytokines, respectively, in the alveolar spaces, as measured by ELISA. A temporal observation of enhanced NKT (CD3-CD19-CD1d+) cell response was also determined by FACS. In addition, FACS revealed that RSV infection of NKT cell knock out (CD1d-/-) neonatal mouse had lower proportions of pDCs and a higher proportions of mDCs compared to the wild type (WT) mouse of same age. Amount of IL-10 in bronchoalveolar lavage fluid was lower in the CD1d-/- mouse than that in the WT mouse. This data suggests that NKT cells are instrumental in skewed polarization of DC in response to RSV infection, which in turn may influence the T cell responses and hence, development of susceptibility to asthma in later life.