Immunological Pathways Triggered byPorphyromonas gingivalisandFusobacterium nucleatum: Therapeutic Possibilities?

Abstract

Porphyromonas gingivalis(P. gingivalis) andFusobacterium nucleatum(F. nucleatum) are Gram-negative anaerobic bacteria possessing several virulence factors that make them potential pathogens associated with periodontal disease. Periodontal diseases are chronic inflammatory diseases of the oral cavity, including gingivitis and periodontitis. Periodontitis can lead to tooth loss and is considered one of the most prevalent diseases worldwide.P. gingivalisandF. nucleatumpossess virulence factors that allow them to survive in hostile environments by selectively modulating the host’s immune-inflammatory response, thereby creating major challenges to host cell survival. Studies have demonstrated that bacterial infection and the host immune responses are involved in the induction of periodontitis. The NLRP3 inflammasome and its effector molecules (IL-1βand caspase-1) play roles in the development of periodontitis. We and others have reported that the purinergic P2X7 receptor plays a role in the modulation of periodontal disease and intracellular pathogen control. Caspase-4/5 (in humans) and caspase-11 (in mice) are important effectors for combating bacterial pathogens via mediation of cell death and IL-1βrelease. The exact molecular events of the host’s response to these bacteria are not fully understood. Here, we review innate and adaptive immune responses induced byP. gingivalisandF. nucleatuminfections and discuss the possibility of manipulations of the immune response as therapeutic strategies. Given the global burden of periodontitis, it is important to develop therapeutic targets for the prophylaxis of periodontopathogen infections.

Dysbiosis of Oral Microbiota During Oral Squamous Cell Carcinoma Development

“…Previously, several models of microbial infection and potential oral microbiome signature link to the pathology of a number of oral diseases including cancer have been established. For example, certain oral bacterial pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum have been reported to disrupt the equilibrium of oral microbiome and along with deregulated immune response eventually initiate periodontal diseases (periodontitis) ( 54 – 56 ). These well studied periodontal organisms subsequently prompted researchers to further investigate the precise role of dysbiotic oral micrbiota in developing oral cancer ( 57 , 58 ).…”

The Role of Bacterial and Fungal Human Respiratory Microbiota in COVID-19 Patients

“…P. gingivalis through α 5 β 1-integrin expressed on the epithelial cells, crosses the epithelial barrier, and enters the bloodstream [ 75 ]. LPS from P. gingivalis activates the TLR-4 signaling and triggers the secretion of IL-1 β and IL-6 [ 76 , 77 ]. TLR-4 signaling activated by Pg is also reported to be associated with human pancreatic tumors [ 78 ].…”

Involvement of Cathepsins in Innate and Adaptive Immune Responses in Periodontitis

“…To date, 11 different TLRs (TLR1-11) have been identified [16]. It has been known that lipopolysaccharides from Porphyromonas gingivalis (P. gingivalis LPS) is recognized by TLR2/TLR4 [19,20] while flagellin in Tannerella forsythia is recognized by TLR5 [21]. e TLR pathway is crucial in the immune responses in periodontitis because TLRs are bound to their corresponding antigens, which triggers intracellular immune responses to produce inflammatory-related mediators [22].…”