The innate host response in caries and periodontitis

Alveolar bone loss is a hallmark of periodontitis progression and its prevention is a key clinical challenge in periodontal disease treatment. Bone destruction is mediated by the host immune and inflammatory response to the microbial challenge. However, the mechanisms by which the local immune response against periodontopathic bacteria disturbs the homeostatic balance of bone formation and resorption in favour of bone loss remain to be established. The osteoclast, the principal bone resorptive cell, differentiates from monocyte/macrophage precursors under the regulation of the critical cytokines macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. TNF-α, IL-1, and PGE2 also promote osteoclast activity, particularly in states of inflammatory osteolysis such as those found in periodontitis. The pathogenic processes of destructive inflammatory periodontal diseases are instigated by subgingival plaque microflora and factors such as lipopolysaccharides derived from specific pathogens. These are propagated by host inflammatory and immune cell influences, and the activation of T and B cells initiates the adaptive immune response via regulation of the Th1-Th2-Th17 regulatory axis. In summary, Th1-type T lymphocytes, B cell macrophages, and neutrophils promote bone loss through upregulated production of proinflammatory mediators and activation of the RANK-L expression pathways.

Immune cell populations in the skin are predominantly comprised of dendritic cells (DCs) and macrophages. A lack of consensus regarding how to define these cell types has hampered research in this area. In this Review, we focus on recent advances that, based on ontogeny and global gene-expression profiles, have succeeded in discriminating DCs from macrophages in the skin. We discuss how these studies have enabled researchers to revisit the origin, diversity and T cell-stimulatory properties of these cells, and have led to unifying principles that extend across tissues and species. By aligning the DC and macrophage subsets that are found in mouse skin with those that are present in human skin, these studies also provide crucial information for developing intradermal vaccines and for managing inflammatory skin conditions.

Chronic adult periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissue and bone that support teeth. Concepts of the specific mechanisms involved in the disease have evolved with new technologies and knowledge. Histopathologic observations of diseased human tissues were used previously to speculate on the causes of periodontitis and to describe models of pathogenesis. Experimental evidence later emerged to implicate bacterial plaque deposits as the primary factor initiating periodontitis. At the same time, specific bacteria and immunoinflammatory mechanisms were differentially implicated in the disease. In the mid-1990s, early insights about complex diseases, such as periodontitis, led to new conceptual models of the pathogenesis of periodontitis. Those models included the bacterial activation of immunoinflammatory mechanisms, some of which targeted control of the bacterial challenge and others that had adverse effects on bone and connective tissue remodeling. Such models also acknowledged that different environmental and genetic factors modified the clinical phenotype of periodontal disease. However, the models did not capture the dynamic nature of the biochemical processes, i.e., that innate differences among individuals and changes in environmental factors may accelerate biochemical changes or dampen that shift. With emerging genomic, proteomic, and metabolomic data and systems biology tools for interpreting data, it is now possible to begin describing the basic elements of a new model of pathogenesis. Such a model incorporates gene, protein, and metabolite data into dynamic biologic networks that include disease-initiating and -resolving mechanisms. This type of model has a multilevel framework in which the biochemical networks that are regulated by innate and environmental factors can be described and the interrelatedness of networks can be captured. New models in the next few years will be merely frameworks for integrating key knowledge as it becomes available from the "-omics" technologies. However, it is possible to describe some of the key elements of the new models and discuss distinctions between the new and older models. It is hoped that improved conceptual models of pathogenesis will assist in focusing new research and speed the translation of new data into practical applications.