Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathways

Eur J Immunol. 2002 Apr;32(4):1188-95. doi: 10.1002/1521-4141(200204)32:4<1188::AID-IMMU1188>3.0.CO;2-A.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Proteins*
  • Adult
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Chlamydophila pneumoniae / chemistry
  • Chlamydophila pneumoniae / physiology*
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Drosophila Proteins*
  • Gene Expression Regulation*
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharide Receptors / physiology
  • Macrophages, Peritoneal / physiology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Sonication
  • Specific Pathogen-Free Organisms
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Cytokines
  • Drosophila Proteins
  • Interleukin-1
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide-binding protein
  • Interleukin-10