title: Neisseria gonorrhoeae triggers the PGE2/IL-23 pathway and promotes IL-17 production by human memory T cells.
abstract: PGE2 is a potent modulator of the T helper (Th)17 immune response that plays a critical role in the host defense against bacterial, fungal and viral infections. We recently showed high serum levels of interleukin (IL)-17 in patients with gonococcal infection and we hypothesized that Neisseria gonorrhoeae could exploit a PGE2 mediated mechanism to promote IL-17 production. Here we show that N. gonorrhoeae induces human dendritic cell (DC) maturation, secretion of prostaglandin E2 and proinflammatory cytokines, including the pro-Th17 cytokine IL-23. Blocking PGE2 endogenous synthesis selectively reduces IL-23 production by DC in response to gonococcal stimulation, confirming recent data on PGE2/IL-23 crosstalk. N. gonorrhoeae stimulated DC induce a robust IL-17 production by memory CD4(+) T cells and this function correlates with PGE2 production. Our findings delineate a previously unknown role for PGE2 in the immune response to N. gonorrhoeae, suggesting its contribute via Th17 cell expansion.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. paola.stefanelli@iss.it
authors.forename: Paola
authors.initials: P
authors.lastname: Stefanelli
authors.forename: Raffaela
authors.initials: R
authors.lastname: Teloni
authors.forename: Anna
authors.initials: A
authors.lastname: Carannante
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mariotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Nisini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gagliardi
mesh_terms: D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D006069:Gonorrhea / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D015232:Dinoprostone