Role of gingipains in protection of Porphyromonas gingivalis from macrophage clearence

Porphyromonas gingivalis (Pg) is a pathogen commonly found in the oral cavity, within the dental plaque biofilm. Along with other pathobionts, Pg plays a key role in periodontitis, a condition where bacterial-driven chronic inflammation leads to the destruction of tooth-supporting structures and eventual tooth loss. From inflamed gums , Pg can enter the bloodstream and has been detected in atherosclerotic plaques. Substantial evidence now links Pg to cardiovascular and neurodegenerative diseases.

In this study, we used transgenic zebrafish with fluorescently labeled macrophages and neutrophils to investigate how Pg interacts with phagocytes and evades immune surveillance. Our findings show that macrophages are more effective than neutrophils at phagocytosing and killing Pg, both in circulation and within tissues. In addition, Pg-specific proteases called gingipains significantly impaired phagocytosis and bacterial killing within macrophages, reducing bacterial clearance.

This study sheds light on the innate immune response to Pg and identifies gingipains as potential therapeutic targets for mitigating periodontal-related cardiovascular and neurodegenerative diseases.