Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1

• Neonatal mice are more susceptible than adult mice to mouse adenovirus type 1 (MAV1) respiratory infection.
• We demonstrate that prostaglandin E2 (PGE2) is overproduced in lungs of neonatal mice compared to adults, although not in a virus-specific manner.
• We show that PGE2 is not essential for control of viral replication or induction of inflammatory responses in neonatal mice.
• We also demonstrate that PGE2 does not contribute to the establishment of protective immunity to MAV-1 in neonatal mice.
• Excess PGE2 production therefore does not contribute to age-based differences in susceptibility to MAV-1.

Neonatal mice are more susceptible than adults to mouse adenovirus type 1 (MAV1) respiratory infection. In adult mice, MAV-1 respiratory infection induces production of prostaglandin E2 (PGE2), a lipid mediator that exerts suppressive effects on a variety of host immune functions. We tested the hypothesis that exaggerated PGE2 production in neonatal mice contributes to increased susceptibility to MAV-1. PGE2 concentrations were lower in lungs of uninfected neonatal mice than in adults. PGE2 production was induced by both MAV-1 and a nonspecific stimulus to a greater degree in neonatal mice than in adults, but only in adults was PGE2 induced in a virus-specific manner. Lung viral loads were equivalent in PGE2-deficient neonatal mice and wild type controls, as was virus-induced expression of IFN-γ, IL-17A, and CCL5 in the lungs. PGE2 deficiency had minimal effect on production of virus-specific IgG or establishment of protective immunity in neonatal mice. Collectively, our data indicate that lung PGE2 production is exaggerated early in life, but this effect does not mediate increased susceptibility to MAV-1 infection.