uces PD symptoms in RS 1 ApoEnull mice, and that F. nucleatum is able to spread by hematogenous routes and to modulate host immune response and atherosclerotic risk factors, with evidence for both pro- and anti-inflammatory responses and yet does not promote atherosclerotic lesion progression. Previous in vitro studies showed that F. nucleatum is a potent B cell-mitogen, for which we observe strong evidence in the significantly elevated levels of IgG and IgM during chronic infection of mice. The mitogenic activity is attributed to the outer membrane porin FomA, which is a TLR2 adjuvant. Some of the systemic antibodies to F. nucleatum may provide a protective response, as we detected genomic DNA of F. nucleatum by PCR in fewer systemic organs of 24 week-infected mice than 12-week-infected mice. Oral infection with F. nucleatum significantly altered the serum lipid profile levels. There was evidence for a trend toward a more pro-atherogenic state, by elevating total cholesterol and triglycerides, VLDL and LDL, but also the HDL fraction, which is considered more protective against atheroma formation. HDL is a PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19736355 key molecule with anti-atherogenic properties due to its broad range of functions like reverse cholesterol transport as well as decreasing inflammation, inhibition of thrombosis, stimulation of fibrinolysis, and modulation of immune cells 13 / 19 F. nucleatum Repression of Inflammation in ApoEnull Mice involved in atherosclerosis, especially monocyte-macrophages, B and T lymphocytes. Interestingly, although all of the lipid fractions examined were statistically elevated in F. nucleatum-infected mice, atherosclerotic lesions did not develop. This is in contrast to our observation in P. gingivalis-infected ApoEnull mice, which did not exhibit statistically significantly elevated serum lipoprotein particle fractions, yet developed significant atherosclerotic lesions, and T. denticola-infected ApoEnull mice, which exhibited significantly elevated cholesterol and VLDL and developed significant plaque lesions. It is possible that the significant increase in serum HDL observed with oral F. nucleatum infection is sufficient to counter the effects of hyperlipidemia, so that the lipid shift, while apparently pro-atherogenic, has a net zero effect on the mouse vasculature. Additionally, our previous monoinfection studies with P. gingivalis or T. denticola significantly elevated the serum oxyLDL, a particular risk factor for atherosclerosis, yet the data presented here demonstrate elevated oxyLDL alone to be insufficient to induce significant atherosclerotic plaque growth. These apparently contradictory findings demonstrate differences in the ability of different bacterial species to induce atherosclerotic plaque development. Notable difference between F. nucleatum 
monoinfection and the recently published P. gingivalis and T. denticola monoinfection studies is that serum NO was not significantly decreased in F. nucleatum-infected mice as it was in the P. gingivalis and T. denticola monoinfections. Decreased serum NO is an indicator of endothelial dysfunction, which is thought to contribute to atherosclerotic lesion initiation. As both the P. gingivalis and T. denticola monoinfected mice demonstrated significant atherosclerotic PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19735871 plaque accumulation, while F. nucleatum monoinfected mice did not, we hypothesize that bacterial-induced endothelial dysfunction may be an important mediator of infection-induced atherosclerotic plaque development. F. nucleatum