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Review
. 2013 Jun;62(1):163-202.
doi: 10.1111/prd.12005.

Periodontal disease immunology: 'double indemnity' in protecting the host

Jeffrey L Ebersole, Dolphus R Dawson 3rd, Lorri A Morford, Rebecca Peyyala, Craig S Miller, Octavio A Gonzaléz
Review

Periodontal disease immunology: 'double indemnity' in protecting the host

Jeffrey L Ebersole et al. Periodontol 2000. 2013 Jun.

Abstract

During the last two to three decades our understanding of the immunobiology of periodontal disease has increased exponentially, both with respect to the microbial agents triggering the disease process and the molecular mechanisms of the host engagement maintaining homeostasis or leading to collateral tissue damage. These foundational scientific findings have laid the groundwork for translating cell phenotype, receptor engagement, intracellular signaling pathways and effector functions into a 'picture' of the periodontium as the host responds to the 'danger signals' of the microbial ecology to maintain homeostasis or succumb to a disease process. These findings implicate the chronicity of the local response in attempting to manage the microbial challenge, creating a 'Double Indemnity' in some patients that does not 'insure' health for the periodontium. As importantly, in reflecting the title of this volume of Periodontology 2000, this review attempts to inform the community of how the science of periodontal immunology gestated, how continual probing of the biology of the disease has led to an evolution in our knowledge base and how more recent studies in the postgenomic era are revolutionizing our understanding of disease initiation, progression and resolution. Thus, there has been substantial progress in our understanding of the molecular mechanisms of host-bacteria interactions that result in the clinical presentation and outcomes of destructive periodontitis. The science has embarked from observations of variations in responses related to disease expression with a focus for utilization of the responses in diagnosis and therapeutic outcomes, to current investigations using cutting-edge fundamental biological processes to attempt to model the initiation and progression of soft- and hard-tissue destruction of the periodontium. As importantly, the next era in the immunobiology of periodontal disease will need to engage more sophisticated experimental designs for clinical studies to enable robust translation of basic biologic processes that are in action early in the transition from health to disease, those which stimulate microenvironmental changes that select for a more pathogenic microbial ecology and those that represent a rebalancing of the complex host responses and a resolution of inflammatory tissue destruction.

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Figures

Fig. 1
Fig. 1
Phenotypes of macrophages with varied stimuli and functional capacity that affect the characteristics of host responses. EGF, epidermal growth factor; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFNγ, interferon gamma; IL, interleukin; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MHC, major histocompatibility complex; NO, nitric oxide; PDGF, platelet-derived growth factor; ROS, reactive oxygen species; TGFβ, transforming growth factor-beta; TNFα, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor; VitD, vitamin D3; YM-1, eosinophil chemotactic factor-L.
Fig. 2
Fig. 2
Dendritic cell interactions with various types of oral bacteria, and potential outcomes of dendritic cell functional development that could contribute to discrimination among commensals and pathogens. iDC, immature dendritic cell; Fn, Fusobacterium nucleatum; IFNγ, interferon gamma; IL, interleukin; mDC, mature dendritic cell; Pg, Porphyromoas gingivalis; Sg, Streptococcus gordonii; Th, T helper cell.
Fig. 3
Fig. 3
Considerations for multispecies biofilms of oral bacteria interacting with epithelial cells and potential for resulting differential characteristics of subsequent innate immune and/or inflammatory responses. RGPL, rigid gas-permeable hard contact lens.
Fig. 4
Fig. 4
Model of the RANK/RANKL/osteoprotegerin pathway for osteoclastic alveolar bone loss in periodontal disease. Also shown are potential sites for blocking these deleterious reactions with various ‘biologicals’ based upon receptor–ligand engagement and intracellular signaling pathways. OPG, osteoprotegerin.
Fig. 5
Fig. 5
Schematic of inflammasome with identification of various microbial products that have been shown to interact with various nucleotide-binding and oligomerization domains and resulting types of downstream responses. Adapted from Zaki et al., 2011 (360). ASC, apoptosis-associated speck-like protein containing a CARD; CARD, caspase-recruitment domain; IFN-γ, interferon gamma; IL, interleukin; NF-κB, nuclear factor of kappa light polypeptide gene enhancer in B-cells; NLRC, nucleotide oligomerization domain with caspase recruitment domain receptors; NLRP, nucleotide oligomerization domain with pyrin domain receptors; NOD, nucleotide-binding and oligomerization domain; PAMP, pathogen-associated molecular pattern; PGN, peptidoglycan; RICK, receptor interacting serine threonine kinase 2; TGFβ, transforming growth factor-beta; TLR, toll-like receptor; TNFα, tumor necrosis factor-alpha.
Fig. 6
Fig. 6
Schematic of considerations of potential biomarker targets for salivary diagnostic panels for periodontal disease. GM-CSF, granulocyte–macrophage colony-stimulating factor; IL, interleukin; MCP-1, monocyte chemotactic protein 1; Mip-1α, macrophage inflammatory protein-1alpha; MMP, matrix metalloproteinase; PGE2, prostaglandin E2; TIMP, tissue inhibitor of metalloproteinase.
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