PMC

Colonization by P. gingivalis impairs innate immunity by subverting complement-TLR crosstalk, leading to increased numbers of periodontal bacteria and therefore enhanced inflammation through the activation of synergistic complement and TLR pathways. The inflammatory environment is favorable to further bacterial growth, since the gingival inflammatory exudate is a rich source of nutrients (e.g., degraded host proteins and hemin, a source of essential iron). These environmental changes, moreover, can alter the composition of the oral microbiota, favoring those bacteria (e.g., proteolytic and asaccharolytic organisms) that can better exploit these environmental changes. These changes result in even higher inflammation and bone resorption, leading to increased niche space (deeper periodontal pockets) for the bacteria, thereby perpetuating a vicious cycle of periodontal tissue destruction. Adapted from Hajishengallis et al (ref. ).

P. gingivalis exploits C5aR signaling and inhibits the host defense, leading to an altered composition and increased numbers of the periodontal microbiota which, in turn, cause complement-dependent periodontal inflammation and bone loss. This community-wide effect can occur at low colonization levels of P. gingivalis and requires its Arg-specific gingipain activity, acting in a C5 convertase-like manner and thus cleaving C5 and generating high levels of C5a locally. C5a-induced activation of C5aR triggers inflammation and is also crucially involved in subversive crosstalk with the TLR2/1 complex that impairs macrophage killing. The ability of P. gingivalis to orchestrate inflammatory disease by remodeling a symbiotic microbiota into a dysbiotic state, while being a minor constituent of this community, qualifies it as a keystone pathogen. This pathologic process is reversible, since C5aR blockade promotes the clearance of P. gingivalis and reverses its dysbiotic effects. Adapted from Hajishengallis et al (ref. ).