Chronic infection and inflammation of the gums, peridontitis, is associated with increased risk of atherosclerosis, a clogging of the arteries. This is because inflammation spreads beyond the mouth, and the process of inflammation in artery walls over the long term contributes to the production of plaques of dead cells and metabolic waste. Here researchers look into the details of this link between the two conditions:
Chronic oral infection with the periodontal disease pathogen, Porphyromonas gingivalis, not only causes local inflammation of the gums leading to tooth loss but also is associated with an increased risk of atherosclerosis. Like other gram-negative bacteria, P. gingivalis has an outer layer that consists of sugars and lipids. The mammalian immune system has evolved to recognize parts of this bacterial coating, which then triggers a multi-pronged immune reaction. As part of the "arms race" between pathogens and their hosts, several types of gram-negative bacteria, including P. gingivalis, employ strategies by which they alter their outer coats to avoid the host immune defense.
[The researchers] focused on the role of a specific lipid expressed on the outer surface of P. gingivalis, called lipid A, which is known to interact with a key regulator of the host's immune system called TLR4. P. gingivalis can produce a number of different lipid A versions, and the researchers wanted to clarify how these modify the immune response and contribute to the ability of the pathogen to survive and cause inflammation - both locally, resulting in oral bone loss, and systemically, in distant blood vessels.
They constructed genetically modified strains of P. gingivalis with two distinct lipid A versions. The resulting bacteria produced either lipid A that activated TLR4 (called "agonist") or lipid A that interacted with TLR4 but blocked activation ("antagonist"). Utilizing these strains, they demonstrate that P. gingivalis production of antagonist lipid A renders the pathogen resistant to host bacterial killing responses. This facilitates bacterial survival in macrophages, specific immune cells that normally not only gobble up the bacteria but also "digest" and kill them.
When the researchers infected atherosclerosis-prone mice with the P. gingivalis TLR4 antagonist strain, they found that this exacerbates inflammation in the blood vessels and promotes atherosclerosis. In contrast, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A variations, which demonstrates that there are distinct mechanisms for induction of local versus systemic inflammation.