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 E-2 (PGE(2)). PGE(2) modifies the production of an immune response by altering DC function through PGE(2) receptors. PGE(2) 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 PGE(2) 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 PGE(2)in 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 PGE(2) increased other costimulatory molecules and C-type lectins. Also, exposure of PGE(2) to infected cDCs increased Fc gamma RIII and Fc gamma RIIb, suggesting that PGE(2) 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 PGE(2) drives production of a diverse adaptive immune response with implications for regulating tissue inflammation.