title: Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathways.
abstract: Recent studies suggest that infection with Chlamydia pneumoniae is associated with atherosclerosis, and that cytokines play an important role in the initiation and progression of Chlamydia-induced inflammation. When freshly isolated peripheral blood mononuclear cells (PBMC) were stimulated for 24 h with sonicated C. pneumoniae, significant amounts of the pro-inflammatory cytokines TNF-alpha and IL-1beta and of the anti-inflammatory cytokine IL-10 were released into the supernatant. The addition of serum increased cytokine release induced by C. pneumonia two- to fivefold (p < 0.01). This effect was not due to complement, mannose-binding lectin (MBL) or lipopolysaccharide-binding protein (LBP). Incubation of PBMC with either anti-Toll-like receptor 4 (TLR4) or anti-CD14 blocking antibodies did not influence the production of cytokines induced by Chlamydia. The induction of cytokines by C. pneumoniae in macrophages from C3H / HeJ mice, known to have a defective TLR4, was identical to that measured in control macrophages from C3H / HeN mice. In contrast, incubation of PBMC with an anti-TLR2 blocking antibody significantly inhibited the production of TNF by 67 % and of IL-1beta by 72 %. In conclusion, C. pneumoniae stimulates cytokine production in a serum-dependent manner, but independently of complement, MBL and LBP. C. pneumoniae induces the pro-inflammatory cytokines TNF and IL-1beta through TLR2, but not TLR4 and CD14.
authors.affiliation: Department of Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands. M.Netea@aig.azn.nl
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
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: D000209:Acute-Phase Proteins; D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000737:chemistry / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013010:Sonication; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D029721:Drosophila Proteins; D007375:Interleukin-1; D016753:Interleukin-10; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human