Complement and periodontitis.
Although the complement system is centrally involved in host defense, its overactivation or deregulation (e.g., due to inherent host genetic defects or due to pathogen subversion) may excessively amplify inflammation and contribute to immunopathology. Periodontitis is an oral infection-driven chronic inflammatory disease which exerts a systemic impact on health. This paper reviews evidence linking complement to periodontal inflammation and pathogenesis. Clinical and histological observations show a correlation between periodontal inflammatory activity and local complement activation. Certain genetic polymorphisms or deficiencies in specific complement components appear to predispose to increased susceptibility to periodontitis. Animal model studies and in vitro experiments indicate that periodontal bacteria can either inhibit or activate distinct components of the complement cascade. Porphyromonas gingivalis, a keystone species in periodontitis, subverts complement receptor 3 and C5a anaphylatoxin receptor signaling in ways that promote its adaptive fitness in the presence of non-productive inflammation. Overall, available evidence suggests that complement activation or subversion contributes to periodontal pathogenesis, although not all complement pathways or functions are necessarily destructive. Effective complement-targeted therapeutic intervention in periodontitis would require determining the precise roles of the various inductive or effector complement pathways. This information is essential as it may reveal which specific pathways need to be blocked to counteract microbial evasion and inflammatory pathology or, conversely, kept intact to promote host immunity.
Hajishengallis
George
G
Department of Microbiology and Immunology, University of Louisville School of Dentistry, Loueisville, KY 40292, USA. g0haji01@louisville.edu
D000818:Animals; D003167:Complement Activation; D015936:Complement C5a / Q000502:physiology; D051056:Complement Inactivating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003165:Complement System Proteins / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D016177:Macrophage-1 Antigen / Q000502:physiology; D058990:Molecular Targeted Therapy; D010518:Periodontitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction
D051056:Complement Inactivating Agents; D016177:Macrophage-1 Antigen; D044087:Receptor, Anaphylatoxin C5a; D015936:Complement C5a; D003165:Complement System Proteins