Pathogen-mediated Inflammatory Atherosclerosis Is Mediated in Part via Toll-like Receptor 2-induced Inflammatory Responses

J Innate Immun. 2010;2(4):334-43. doi: 10.1159/000314686. Epub 2010 May 10.


Studies in humans have established that polymorphisms in genes encoding the innate immune Toll-like receptors (TLRs) are associated with inflammatory atherosclerosis. In hyperlipidemic mice, TLR2 and TLR4 have been reported to contribute to atherosclerosis progression. Human and mouse studies support a role for the oral pathogen Porphyromonas gingivalis in atherosclerosis, although the mechanisms by which this pathogen stimulates inflammatory atherosclerosis via innate immune system activation is not known. Using a genetically defined apolipoprotein E-deficient (ApoE(-/-)) mouse model we demonstrate that pathogen-mediated inflammatory atherosclerosis occurs via both TLR2-dependent and TLR2-independent mechanisms. P. gingivalis infection in mice possessing functional TLR2 induced the accumulation of macrophages as well as inflammatory mediators including CD40, IFN-gamma and the pro-inflammatory cytokines IL-1 beta, IL-6 and tumor necrosis factor-alpha in atherosclerotic lesions. The expression of these inflammatory mediators was reduced in atherosclerotic lesions from P. gingivalis-infected TLR2-deficient (TLR2(-/-)) mice. These studies provide a mechanistic link between an innate immune receptor and pathogen-accelerated atherosclerosis by a clinically and biologically relevant bacterial pathogen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / immunology
  • Apolipoproteins E / metabolism
  • Atherosclerosis* / immunology
  • Atherosclerosis* / microbiology
  • Atherosclerosis* / physiopathology
  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / microbiology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Humans
  • Inflammation / immunology*
  • Inflammation / microbiology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Porphyromonas gingivalis / immunology
  • Porphyromonas gingivalis / pathogenicity*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism*


  • Apolipoproteins E
  • Cytokines
  • Inflammation Mediators
  • Toll-Like Receptor 2