title: Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation.
abstract: Pseudomonas aeruginosa releases a wide array of toxins and tissue-degrading enzymes. Production of these malicious virulence factors is controlled by interbacterial communication in a process known as quorum sensing. An increasing body of evidence reveals that the bacterial signal molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) exhibits both quorum-sensing signalling and immune-modulating properties. Recently, yet another quorum-sensing signal molecule, the Pseudomonas quinolone signal (PQS), has been shown to affect cytokine release by mitogen-stimulated human T cells. In the present article we demonstrate that both OdDHL and PQS decrease the production of interleukin-12 (IL-12) by Escherichia coli lipopolysaccharide-stimulated bone marrow-derived dendritic cells (BM-DCs) without altering their IL-10 release. Moreover, BM-DCs exposed to PQS and OdDHL during antigen stimulation exhibit a decreased ability to induce T-cell proliferation in vitro. Collectively, this suggests that OdDHL and PQS change the maturation pattern of stimulated DCs away from a proinflammatory T-helper type I directing response, thereby decreasing the antibacterial activity of the adaptive immune defence. OdDHL and PQS thus seem to possess dual activities in the infection process: as inducers of virulence factors as well as immune-modulators facilitating the infective properties of this pathogen.
authors.affiliation: Center for Biomedical Microbiology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Mette E
authors.initials: ME
authors.lastname: Skindersoe
authors.forename: Louise H
authors.initials: LH
authors.lastname: Zeuthen
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.forename: Lisbeth N
authors.initials: LN
authors.lastname: Fink
authors.forename: James
authors.initials: J
authors.lastname: Lazenby
authors.forename: Christine
authors.initials: C
authors.lastname: Whittall
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Diggle
authors.forename: Hanne
authors.initials: H
authors.lastname: Froekiaer
authors.forename: Margaret
authors.initials: M
authors.lastname: Cooley
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism; D015363:Quinolones / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D007155:Immunologic Factors; C109860:N-(3-oxododecanoyl)homoserine lactone; D015363:Quinolones; D006714:Homoserine; D015107:4-Butyrolactone