Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice

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Abstract

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.

Methods and 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.

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