Increased PGD2 is associated with delayed dendritic cell maturation in neonates during respiratory viral infection (VIR2P.1031)

Abstract

Abstract During respiratory viral infection in adults, inflammatory cytokines stimulate conventional dendritic cells (cDC) to increase expression of MHC class II molecules, co-stimulatory molecules, and chemokine receptors. Activated cDC then migrate from the lung to the draining lymph nodes where they present antigen to T cells. Our previous studies demonstrated that neonatal mice exhibit reduced inflammation and inflammatory cytokine expression during paramyxoviral infection. Thymic stromal lymphopoietin (TSLP), a cytokine known to participate in cDC activation, is expressed at significantly lower levels in neonatal mice during respiratory viral infection compared to adults. Thus, we hypothesized that cDC maturation and migration to lymph nodes may be delayed or impaired in neonates. Adult and two-day old neonatal C57BL/6 mice were inoculated intranasally with Sendai virus (500 pfu/g body weight). Adult cDC had increased expression of MHC Class II and CCR7 and had migrated to the lymph nodes on post-infection days 1 and 3. However, these events were delayed in neonates and did not reach adult levels until post-infection day 7. Interestingly, studies in geriatric mice suggest that high levels of Prostaglandin D2 (PGD2) may inhibit cDC maturation and migration to lymph nodes. We also observed higher PGD2 expression in neonatal bronchoalveolar lavage fluid compared to adults during paramyxoviral infection, and this may contribute to the impairment of DC maturation in neonates.