Endogenous PGE2 promotes the induction of human Th17 responses by fungal β-glucan

The interaction of PAMPs with cells of the innate immune system shapes the adaptive host response. Here, we report that beta-glucan, a major fungal PAMP purified from Candida albicans, stimulates human DCs to secrete a pro-Th17 cytokine pattern. Notably, beta-glucan induces PGE2 production, which has been shown to play a pivotal role in Th17 cell expansion. Inhibition of PGE2 synthesis or blockade of PGE2 receptors EP2 and EP4 drastically reduces IL-23 production by beta-glucan-activated DCs, suggesting that endogenous PGE2 amplifies IL-23 synthesis in response to the C. albicans PAMP. Moreover beta-glucan promotes the expansion of Th17 cells, which is strongly decreased by EP2 and EP4 receptor blockade on DCs. Our results highlight a novel role for PGE2 in the regulation of innate and adaptive immune response triggered by recognition of a prominent, highly conserved fungal PAMP such as beta-glucan. J. Leukoc. Biol. 88: 947-954; 2010.