title: The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14.
abstract: Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1beta, TNF-alpha, IL-6, and IL-8. rMip proinflammatory activity could not be attributed to Escherichia coli LPS contamination as determined by the Limulus Amoebocyte lysate assay, insensitivity to polymyxin B (50 microg/ml), and different serum requirement. We have recently demonstrated that Mip is a "classical" bacterial lipoprotein, exposed at the surface of EB. The proinflammatory activity of EB was significantly attenuated in the presence of polyclonal Ab to rMip. Native Mip was able to induce TNF-alpha and IL-8 secretion, whereas a nonlipidated C20A rMip variant was not. Proinflammatory activity of rMip was unaffected by heat or proteinase K treatments but was greatly reduced by treatment with lipases, supporting a role of lipid modification in this process. Stimulating pathways appeared to involve TLR2/TLR1/TLR6 with the help of CD14 but not TLR4. These data support a role of Mip lipoprotein in pathogenesis of C. trachomatis-induced inflammatory responses.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University Hospital, and Department of Pathology and Immunology, Geneva Medical School, Switzerland. sylvette.bas@hcuge.ch
authors.forename: Sylvette
authors.initials: S
authors.lastname: Bas
authors.forename: Laurence
authors.initials: L
authors.lastname: Neff
authors.forename: Madeleine
authors.initials: M
authors.lastname: Vuillet
authors.forename: Ursula
authors.initials: U
authors.lastname: Spenato
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051194:Toll-Like Receptor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000906:Antibodies; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008074:Lipoproteins; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha