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Oral bacteria and increased atherosclerosis risk
A new study supports the idea that good oral hygiene can help protect against cardiovascular disease risk. The oral anaerobic bacteria Porphyromonas gingivalis can evade host immune recognition and increase systemic inflammation and increased atherosclerosis risk by altering a surface molecule called lipid A so that it blocks activation of a key host immune receptor called toll-like receptor 4 (TLR-4). This results in an attenuated production of anti-bacterial inflammatory cytokines by the host and allows the bacteria to survive in macrophages, host cells that normally ingest and kill bacteria. These are the main findings of a new paper in the journal PLoS Pathogens from researchers in Boston University School of Medicine and the University of Washington.

P. gingivalis is an oral gram negative bacteria that causes local inflammation, resulting in destruction of tissues that support the teeth and resorption of bone. However, it is also associated with increased systemic inflammation with increased risk of diseases including diabetes and cardiovascular disease. It has been detected in atherosclerotic lesions in humans and has been shown to increase atherosclerosis in animal models. In the current study, the researchers sought to determine the mechanism behind this increased systemic inflammation and atherosclerosis. The results indicated that the mechanism behind systemic inflammation differed from that underlying local inflammation.

In common with other gram-negative bacteria, P. gingivalis expresses a protein called lipid A, which is the part of the lipopolysaccharide in the bacterial cell wall recognised by the key host TLR-4 immune receptor. Recognition of lipid A by TLR-4 initiates an immediate immune response characterised by release of pro-inflammatory cytokines and bacterial ingestion and killing by host macrophages. However, many bacteria have evolved strategies to modify lipid A and evade host recognition via TLR-4. P. gingivalis produces a number of modified lipid A structures, some of which are antagonistic to TLR-4 or induce no response from the receptor. The current study shows that the increased systemic inflammation and atherosclerosis induced by P. gingivalis involves the modified lipid A structures.

The research team used modified strains of P. gingivalis incorporating distinct lipid A versions, one of which activated TLR-4 (agonist) and one of which inhibited TLR-4 activation (antagonist). They used these P. gingivalis strains to infect a mouse model which was prone to atherosclerosis. The results indicated that use of the antagonist P. gingivalis strain resulted in reduced production of pro-inflammatory mediators and bacterial survival in macrophages with chronic vascular inflammation. By contrast, infection with the agonist P. gingivalis strain increased the production of proinflammatory mediators and macrophage killing of bacteria. The results also indicated that lipid A variations had no impact on the local response leading to oral tissue and bone damage, indicating that this is mediated by a separate mechanism.

The researchers conclude, “P gingivalis modifies its lipid A structure in order to evade host defenses and establish chronic infection leading to persistent systemic low-grade inflammation…uniquely among gram-negative pathogens, P. gingivalis evasion of TLR4-mediated host immunity results in progression of inflammation at a site that is distant from local infection by gaining access to the vasculature.”


Slocum C, Coats SR, Hua N, Kramer C, Papadopoulos G, et al. (2014) Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation. PLoS Pathog 10(7): e1004215. doi:10.1371/journal.ppat.1004215;
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