Prostaglandin D2 Levels Regulate CD103+ Conventional Dendritic Cell Activation in Neonates During Respiratory Viral Infection

During respiratory viral infection, conventional dendritic cells (cDCs) take up antigen and migrate to the draining lymph nodes to present viral antigen and activate cytotoxic T lymphocytes; however, regulation of cDC activation and migration may be age dependent. In this study, we used a mouse model of paramyxoviral infection (Sendai virus) and demonstrated that cDCs, which have migrated from lungs to the draining lymph nodes, are delayed in expressing activation markers in neonatal mice compared with adults. Neonatal lung cDCs expressed reduced levels of MHC Class II (major histocompatibility complex II) and CCR7 (chemokine receptor type 7) on postinfection days 3 and 5, respectively. The level of the CCR7 ligand CCL19 was significantly reduced in neonatal lungs during the course of viral infection. Interestingly, the arachidonic acid metabolite prostaglandin D-2 (PGD(2)) was present at significantly higher levels in neonatal bronchoalveolar lavage fluid compared with adults. This was associated with increased expression of lipocalin PGD(2) synthase mRNA levels in neonatal lungs and in isolated neonatal tracheal epithelial cells. Although thymic stromal lymphopoietin (TSLP) expression has been associated with increased PGD(2) production, we found that TSLP levels were reduced in neonatal lungs. Importantly, blocking PGD(2) function using a prostaglandin D-2 receptor 1 (DP1) antagonist restored cDC activation in neonates. Together, these data suggest that cDC activation in neonates is delayed by a PGD(2) mechanism and associated decreased chemokine signals.