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Pathogen-mediated inflammatory atherosclerosis is mediated in part via Toll-like receptor 2-induced inflammatory responses.
- Source :
-
Journal of innate immunity [J Innate Immun] 2010; Vol. 2 (4), pp. 334-43. Date of Electronic Publication: 2010 May 10. - Publication Year :
- 2010
-
Abstract
- 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.<br /> ((c) 2010 S. Karger AG, Basel.)
- Subjects :
- Animals
Apolipoproteins E deficiency
Apolipoproteins E genetics
Apolipoproteins E immunology
Apolipoproteins E metabolism
Bacteroidaceae Infections immunology
Bacteroidaceae Infections microbiology
Disease Models, Animal
Humans
Inflammation microbiology
Inflammation Mediators immunology
Inflammation Mediators metabolism
Macrophages immunology
Male
Mice
Mice, Inbred C57BL
Porphyromonas gingivalis immunology
Toll-Like Receptor 2 genetics
Toll-Like Receptor 2 immunology
Atherosclerosis immunology
Atherosclerosis microbiology
Atherosclerosis physiopathology
Cytokines metabolism
Inflammation immunology
Porphyromonas gingivalis pathogenicity
Toll-Like Receptor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1662-8128
- Volume :
- 2
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of innate immunity
- Publication Type :
- Academic Journal
- Accession number :
- 20505314
- Full Text :
- https://doi.org/10.1159/000314686