Age‐Dependent Differential Polarization of Lung Dendritic Cells in Response to RSV infection

Abstract

Bronchiolitis and pneumonia due to RSV infection result in significant number of pediatric hospitalization in the United States. The survivors develop airway hyper‐responsiveness (AHR) and wheezing in later life. A predominant Th2 response prevails in the respiratory tract of these individuals. Development of Th1 vs. Th2 responses largely depends on the nature of antigen and the type of antigen presenting cell (APC) involved. Dendritic cells (DC) are the major APC in the respiratory tract. In the present studies, using a mouse model, we examined whether young infants respond differently to RSV infection than adults, which may explain their post‐RSV‐infection susceptibility to asthma. Flow cytometry revealed that the proportions of myeloid DC (mDCs; CD11blo CD11chi/med CD45R−) to plasmacytoid DCs (pDCs; CD11blo CD11clo CD45R+) are different in the pup and adult lungs. We also determined the differential responses of neonatal and adult DCs to RSV infection in regard to expression of MHC and co‐stimulatory molecules. In addition, production of Th1 cytokines were significantly lower and that of Th2 cytokines were higher in the lungs of pups compared to that in adults in response to RSV infection. Thus, different proportions of mDCs to pDCs in the neonatal lungs and inefficient maturation of neonatal lung DCs may underlie the mechanism of differential responses of neonates and adults to RSV as well as development of AHR and susceptibility to asthma.