The finding of UofL School of Dentistry researcher George Hajishengallis and his team appears in the Feb. 16 issue of the journal Science Signaling. The discovery could have implications for treating periodontal disease, an infection that leads to the destruction of gum and bone, causing tooth loss. P. gingivalis also is believed to play a role in heart disease, stroke and other major systemic health problems.
The UofL researchers learned how P. gingivalis hijacks a complement protein, C5, for communication with Toll-like receptors (TLRs). Typically, TLRs notify a white blood cell of bacteria presence and then stimulate the cell to kill the pathogen. Moreover, in its active form, C5 usually functions as a weapon for the host, as it recruits white blood cells that eat and destroy bacteria.
When P.gingivalis begins the hijacking mechanism, it attacks the C5 molecule and selectively generates C5a for manipulation of white blood cells through an undermining communication mechanism between the C5a receptor and TLR2. This impairs the ability of the cells to kill this oral pathogen.
“P. gingivalis is very sophisticated, in that it activates aspects of white blood cell function that will help it and inhibits aspects that hurt it,” Hajishengallis said. “This is the first report of a pathogen capable of proactively instigating and exploiting communication signaling between complement and Toll-like receptors, rather than undermining either system independently. It’s like infiltrating between your enemy’s lines.”
Lab experiments confirm that blocking the C5a receptor inhibits both inflammation and the persistence of P. gingivalis. Hajishengallis and his team hope this mechanism will translate to humans as a way to prevent periodontal and potentially other systemic diseases.
Julie G Heflin