Porphyromonas gingivalis interactions with complement receptor 3 (CR3): innate immunity or immune evasion?
Porphyromonas gingivalis is a major oral pathogen associated with periodontal disease. In this paper, we review the mechanism whereby this organism induces a proadhesive signaling pathway for activation of complement receptor 3 (CR3; CD11b/CD18) and discuss its biological significance on the basis of published findings by our lab and other investigators. The proadhesive pathway is initiated when P. gingivalis fimbriae bind CD14 and activate Toll-like receptor 2 (TLR2)- and phosphatidylinositol 3-kinase-mediated signaling leading to induction of the high-affinity conformation of CR3 in leukocytes. Although this TLR2 proadhesive signaling pathway may normally be involved in enhancing leukocyte-endothelial cell interactions and transendothelial migration, intriguing evidence suggests that P. gingivalis has co-opted this pathway for enhancing the interaction of its cell surface fimbriae with CR3. Indeed, activated CR3 interacts with P. gingivalis fimbriae and induces downregulation of interleukin-12 p70, a key cytokine involved in intracellular bacterial clearance. Moreover, the interaction of activated CR3 with P. gingivalis leads to the internalization of the pathogen by macrophages. Since CR3 does not readily activate microbicidal mechanisms and constitutes a "preferred receptor" for certain intracellular pathogens, possible exploitation of CR3 by P. gingivalis for evading innate immune clearance becomes a plausible hypothesis.
Hajishengallis
George
G
Department of Periodontics/Endodondics, Division of Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, KY 40292, USA. g0haji01@louisville.edu
Harokopakis
Evlambia
E
D010861:Fimbriae, Bacterial / Q000502:physiology; D007113:Immunity, Innate; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
D016177:Macrophage-1 Antigen