Periodontal Disease and Gingival Innate Immunity – Who Has the Upper Hand?

Abstract

Dental plaque is a complex microbial biofilm that forms at high cell density in the oral cavity by the successive accumulation of hundreds of different species of bacteria. Both host immune and bacterial factors are involved in the progression from healthy to diseased state in plaque biofilm, and in the oral cavity, gingival epithelial cells (GECs) are one of the first host cell types that encounter colonizing bacteria. As a consequence, GECs respond to the presence of bacteria through an elaborate signaling network, producing antimicrobial peptides (AMPs) and cytokines, leading to host innate immune responses. Periodontal disease is a consequence of the imbalance between the pathogenic potential of the biofilm and host immune defense properties, resulting in an inflammatory reaction of the periodontium. As a part of host defense mechanism, GECs secrete specific endogenous serine protease inhibitors to prevent tissue damage from excessive proteolytic enzyme activity due to inflammation. Recent studies showed GECs induced different serine protease inhibitors in the presence of non-pathogenic bacteria, but these protease inhibitors were attenuated by periopathogens, whose main virulence factors are proteases. Furthermore, periodontal patients with periopathogens present in their plaque exhibited significantly lower protease inhibitors in gingival crevicular fluid in comparison to healthy controls. The degradation of protease inhibitors by periopathogens may result in decreased host protective capacity, and the balance between cellular protease inhibitors and their degradation by periodontal pathogens may be an important factor in susceptibility to breakdown from chronic infection. In addition to bacterial infection, genetic and environmental factors contribute to occurrence and progression of periodontal disease. Recent studies suggest that the manifestation and severity of periodontal disease may be influenced by epigenetic factors. Many patients with the same clinical symptoms respond differently to the same therapy, suggesting the interindividual variability observed as a clinical outcome of the disease is influenced by genetic as well as epigenetic factors. In this chapter, we will closely examine the mechanisms gingival epithelia utilize in inducing AMPs in response to bacterial presence and assess future therapeutic potential of AMPs. We will also focus on the impact the balance between the proteases and protease inhibitors has on oral health and how epigenetic modifications brought on by exposure to periodontal pathogens affect the progression of periodontal disease.