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

Abstract

C. albicans β-glucan induces PGE2 production by human DC and promotes Th17 cell expansion.The interaction of PAMPs with cells of the innate immune system shapes the adaptive host response. Here, we report that β-glucan, a major fungal PAMP purified from Candida albicans, stimulates human DCs to secrete a pro-Th17 cytokine pattern. Notably, β-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 β-glucan-activated DCs, suggesting that endogenous PGE2 amplifies IL-23 synthesis in response to the C. albicans PAMP. Moreover β-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 β-glucan.