Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues

Abstract

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

Keywords: carious lesion; dental pulp; immune response; odontoblast; pulpitis; tertiary dentine.

Figure 1

Anatomy and physiology of the tooth.

Figure 2

The dental pulp. (A) Histology of the dentine-pulp complex (own collection). (B) Odontoblast layer depicted by scanning electron microscopy (modified from [12]).

Figure 3

The carious process (own collection). (A) Extracted tooth with a deep carious lesion: clinical, radiographic and histologic appearance. The carious process has degraded enamel and dentine, which can be seen as radiolucent areas on the radiograph. After Brown and Brenn staining of the same tooth, bacteria are visible in the dentinal tubules (purple). (B) Dentine surface with dentinal tubules in a deep lesion close to the pulp and (C) a shallow cavity. (D) Permeability of dentine represented by hydraulic conductance L_p as a function of thickness for human and bovine dentin. Points with vertical lines represent the means and SD of the original data; lines represent the regressions of y vs. 1/x. (modified from [18]).

Figure 4

Outline of all structural and cellular components involved in the immune defense of the dental pulp.

Figure 5

Apical granuloma developed after pulp necrosis (own collection). (A) H&E staining of granulation tissue with (B) inflammatory cell infiltrates.

Figure 6

Immunological recognition of neoantigens in dysplastic lesions and tumors. Tumor cells, as well as highly dysplastic cells, express neoantigens that can be recognized by immune cells, such as professional antigen-presenting cells (APC). The tumor cells can then be phagocytized, and the antigens are processed and finally presented on major histocompatibility complex (MHC) molecules on T cells. This can initiate an immune reaction against dysplastic cells or cancer cells and therefore prevent the clinical appearance of a cancer disease.