title: Modification of in vivo and in vitro T- and B-cell-mediated immune responses by the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.
abstract: N-3-(oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule of Pseudomonas aeruginosa, plays an important role in the pathogenesis of the organism through its control of virulence factor expression. Several reports have suggested that OdDHL can also directly modulate host immune responses. However, the nature of the modulation is controversial, with different reports suggesting promotion of either humoral (Th2-mediated) or inflammatory (Th1-mediated) responses. This report describes a series of studies which demonstrate for the first time that in vivo administration of OdDHL can modulate the course of an antibody response, with an increase in ovalbumin (OVA)-specific immunogloblulin G1 (IgG1) but not IgG2a in OdDHL-treated OVA-immunized BALB/c mice compared to levels for controls. In vitro stimulation of lymphocytes from both Th1-biased C57Bl/6 and T-cell receptor transgenic mice and Th2-biased BALB/c mice in the presence of OdDHL demonstrated that OdDHL inhibits in vitro cytokine production in response to both mitogen and antigen, with gamma interferon (IFN-gamma) tending to be more inhibited than interleukin-4 (IL-4). In vitro mitogen or antigen restimulation of cells from mice treated with OdDHL in vivo shows effects on cytokine production which depend on the underlying immune bias of the mouse strain used, with a relative increase of IFN-gamma in Th1-biased C57Bl/6 mice and a relative increase of IL-4 in Th2-biased BALB/c mice. Thus, the mode of action of OdDHL on T-cell cytokine production is likely to be a relatively nonspecific one which accentuates an underlying immune response bias rather than one which specifically targets either Th1 or Th2 responses.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia 2052.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ritchie
authors.forename: Andrew O W
authors.initials: AO
authors.lastname: Yam
authors.forename: Kara M
authors.initials: KM
authors.lastname: Tanabe
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rice
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Cooley
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006714:Homoserine / Q000031:analogs & derivatives / Q000633:toxicity*; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014774:Virulence / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D008934:Mitogens; C109860:N-(3-oxododecanoyl)homoserine lactone; D012333:RNA, Messenger; D003208:Concanavalin A; D015847:Interleukin-4; D006714:Homoserine; D007371:Interferon-gamma; D010047:Ovalbumin; D015107:4-Butyrolactone