Enhanced NKT cell response and skewed polarization of DC in RSV infection and susceptibility to asthma (131.6)

Abstract

Abstract RSV infection in early infancy makes individuals susceptible to develop asthma in later life due to airway hyper-responsiveness (AHR) to innocuous antigens, which is characterized by enhanced Th2 responses. Using a neonatal mouse model, we investigated whether differential NKT cell responses and skewed polarization of DC are involved in the underlying mechanism. Flow cytometry revealed a significant increase in the proportions of NKT cells (CD3-CD19-CD1d+) in RSV-infected 5 days old lungs compared to that of 7 and 34 days old lungs. A comparable increase in the proportions of plasmacytoid DCs (pDCs; CD11blo CD11clo CD45R+) to myeloid DC (mDCs; CD11blo CD11chi/med CD45R-) was also determined by flow cytometry. To note, DC phenotypes involved in antigen presentation influence the outcomes of the immune responses. In support of this notion, RSV infection induced a significantly higher production of Th2 cytokines than Th1 cytokines in the lungs of younglings. In contrast, RSV-infected adult lungs produced significantly higher amount of Th1 cytokines. Furthermore, NK cell response was not enhanced in the young lungs as opposed to that in the adult lungs in response to RSV infection. Thus, enhanced NKT cell and reduced NK cell responses to RSV infection in the neonatal lungs, along with an enhanced Th2 response, may have induced a skewed polarization of DCs to pDCs leading to development of AHR and susceptibility to asthma.