title: Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent, TLR2- and TLR4-independent induction of IL-18 release.
abstract: Recent studies suggest that inflammation plays a central role in the pathogenesis of atherosclerosis, and IFN-gamma is a prominent proinflammatory mediator in this context. However, it is unclear what stimuli are responsible for initial stimulation of IFN-gamma synthesis in the vessel wall. In the present study, we demonstrate that Chlamydia pneumoniae is an important stimulus for IFN-gamma synthesis, and this production depends on release of endogenous IL-18, IL-12, and IL-1, but not of TNF. The production of the proinflammatory cytokines TNF and IL-1beta from PBMC by sonicated C. pneumoniae was mediated through TLR2-dependent pathways. In contrast, C. pneumoniae stimulated the production of IL-18 through MyD88-dependent, TLR2-, TLR4-, and CD14-independent pathways, mediated by posttranscriptional mechanisms not involving de novo protein synthesis. In conclusion, C. pneumoniae is a potent stimulus of IFN-gamma production, in addition to the proinflammatory cytokines TNF and IL-1beta, which may contribute to its proatherogenic effects. Most interestingly, C. pneumoniae is also a potent inducer of IL-18 production through pathways independent of TLR2 and TLR4.
authors.affiliation: Department of Medicine, University Medical Center Nijmegen, The Netherlands. M.Netea@aig.umcn.nl
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Liesbeth E H
authors.initials: LE
authors.lastname: Jacobs
authors.forename: Trees J G
authors.initials: TJ
authors.lastname: Verver-Jansen
authors.forename: Johanna
authors.initials: J
authors.lastname: van der Ven-Jongekrijg
authors.forename: Jochem M D
authors.initials: JM
authors.lastname: Galama
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Jos W M
authors.initials: JW
authors.lastname: Van der Meer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D023521:Chlamydophila Infections / Q000378:metabolism*; D016993:Chlamydophila pneumoniae / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D020382:Interleukin-18; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007371:Interferon-gamma