UC Merced

Porphyromonas gingivalis and Fusobacterium nucleatum, Gram-negative anaerobic bacteria, have been identified as major contributing pathogens in the etiology of mild to acute periodontitis. They are opportunistic pathogens that are highly adapted to colonize the oral epithelial tissues. P. gingivalis has also been associated with a variety of other chronic and inflammatory conditions including orodigestive cancers, rheumatoid arthritis, liver disease, and diabetes. Whereas, F. nucleatum has been linked to Lemierre’s syndrome and skin ulcers. Recognition and clearance of these pathogens are regulated by inflammation and host immune response. We aimed to study the mechanisms and inflammatory responses (focusing on the effect with intracellular complexes known as inflammasomes) used by P. gingivalis and F. nucleatum to survive and persist during infection in gingival epithelial cells (GECs). Our findings indicate P. gingivalis infection inhibits inflammasome activation and release of pro-inflammatory cytokines by secretion of nucleoside-diphosphate kinase (NDK) to hydrolyze extracellular ATP. By defining NDK as a key enzyme for influencing inflammation in P. gingivalis infection, therapeutic methods can be designed to possibly target NDK to prevent and treat periodontitis. On the other hand, GECs infected with F. nucleatum induce an opposite immune response of upregulated cytokine production and release as a result of inflammasome activation. In vivo studies with BALB/c and C57BL/6 mice also show pro-inflammatory response during infection. Our findings can be used as a model of invasion during F. nucleatum infection in vitro and in vivo. Expanding our understanding of host response to pathogenic bacteria is important for limiting progression of periodontitis and other emerging systematic disease linked to these bacteria.