A new study has shown that bacteria responsible for many cases of periodontitis causes dysbiosis in a two prong manipulation of the immune system. The researchers say that periodontal bacterium porphyromonas gingivalis acts on two molecular pathways to block immune cells’ killing ability while preserving the cells’ ability to cause inflammation. This protects these bacteria from being removed by the immune system and leads to bone loss and inflammation which is characteristic of periodontitis. The researchers say when inflammation occurs breakdown products are produced which causes dysbiosis and creates a vicious cycle.
P. gingivalis is known as a keystone pathogen. Their presence may be relatively few in the mouth but they can exert a large pull on the overall microbial ecosystem. P. gingivalis doesn’t actually cause periodontitis but is responsible for causing the process that leads to it.
The researchers believe that keystone pathogens like P. gingivalis play a role in other inflammatory disease but this still needs to be researched.
In the study the researchers looked at neutrophils, which carry the bulk of responsibility of responding to periodontal problems. They investigated the role of two protein receptors C5aR and Toll-like receptor-2, or TLR2.
It was found that mice without either receptors and mice treated with drugs that blocked these receptors had lower levels of bacteria when inoculated with P. gingivalis. Furthermore, blocking these receptors on human neutrophils in culture also significantly enhanced the cells’ ability to kill the bacteria. Hence there is some cross talk that occurs between CRaR and TLR2. This cross talk was found in further research to cause degradation of the protein MyD88 which plays a role in clearing infection. Furthermore, they found P. gingivalis actives the enzyme PI3K through this cross talk which promotes inflammation and leads to the neutrophils to not be as effective to phagocytose or eat invading bacteria.
Understanding the various pathways and mechanisms and work with P. gingivalis can play a role in developing new drugs for periodontitis treatment.
Source: Tomoki Maekawa and et al. Porphyromonas gingivalis Manipulates Complement and TLR Signaling to Uncouple Bacterial Clearance from Inflammation and Promote Dysbiosis. Cell Host & Microbe, vol. 15, issue 6, pp. 768, 2014.