Endogenous PGE2 promotes the induction of human Th17 responses by fungal ß-glucan.
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.
Gagliardi
Maria Cristina
MC
Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy.
Teloni
Raffaela
R
Mariotti
Sabrina
S
Bromuro
Carla
C
Chiani
Paola
P
Romagnoli
Giulia
G
Giannoni
Federico
F
Torosantucci
Antonella
A
Nisini
Roberto
R
D000596:Amino Acids / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002176:Candida albicans / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D053759:Interleukin-23 / Q000187:drug effects / Q000235:genetics; D011773:Pyruvates / Q000494:pharmacology; D047071:beta-Glucans / Q000494:pharmacology*
D000596:Amino Acids; D016207:Cytokines; D053759:Interleukin-23; D011773:Pyruvates; D047071:beta-Glucans; D000666:Amphotericin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone