Prostaglandin E₂ modulates dendritic cell function during chlamydial genital infection

Inflammatory responses mediated by antigen-presenting dendritic cells (DCs), can be modulated by the presence of prostaglandins (PG), including prostaglandin E₂ (PGE₂). PGE₂ modifies the production of an immune response by altering DC function through PGE₂ receptors. PGE₂ is produced by epithelial cells lining the murine female reproductive tract during Chlamydia muridarum infection and likely manipulates the antichlamydial immune response during antigen uptake in the genital mucosa. Our data demonstrate that the PGE₂ present locally in the genital tract upon chlamydial genital infection enhanced the recruitment of CD11b⁺ conventional DCs, but not CD45R⁺ plasmacytoid DCs, to infected genital tract tissue and draining lymph nodes in vivo. Furthermore, exposure to PGE₂in vitro during infection of murine bone-marrow-derived conventional DCs (cDCs) boosted interleukin-10 mRNA and protein while not influencing interleukin-12p40 production. Infection of cDCs markedly increased mRNA production of the costimulatory molecules CD86, CD40 and a member of the C-type lectin family, DEC-205, but addition of PGE₂ increased other costimulatory molecules and C-type lectins. Also, exposure of PGE₂ to infected cDCs increased FcγRIII and FcγRIIb, suggesting that PGE₂ enhances the uptake and presentation of C. muridarum and augments production of the antichlamydial adaptive immune response. Taken together, the data suggest that exposure of infected cDCs to PGE₂ drives production of a diverse adaptive immune response with implications for regulating tissue inflammation.