Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice.
BACKGROUND
Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD.


RESULTS
To directly test the connection between periodontal disease and atherosclerosis, apoE-/- mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA-). Both wild-type P gingivalis and the FimA- mutant were detected in blood and aortic arch tissue of apoE-/- mice by PCR after challenge. ApoE-/- mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll-like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA- mutant in the blood and in aortic arch tissue, apoE-/- mice challenged with the FimA- mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis-elicited periodontal disease concomitantly prevents P gingivalis-accelerated atherosclerosis.


CONCLUSIONS
We conclude that invasive P gingivalis accelerates atherosclerosis.
Gibson
Frank C
FC
Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, Mass, USA.
Hong
Charlie
C
Chou
Hsin-Hua
HH
Yumoto
Hiromichi
H
Chen
Jiqiu
J
Lien
Egil
E
Wong
Jodie
J
Genco
Caroline Attardo
CA
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D001161:Arteriosclerosis / Q000276:immunology / Q000382:microbiology*; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000276:immunology; D002478:Cells, Cultured; D010861:Fimbriae, Bacterial / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors