Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

Abstract

The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that α-defensins, β-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment. The oral environmentThe oral cavity is a unique environment. Oral mucosa is a critical protective interface between external and internal environments and must serve as a barrier to the myriad microbial species present in this warm, moist environment. The oral cavity is the only area of the body in which hard tissues break through the epithelial surface. The periodontal epithelium surrounding the tooth is specialized to form an attachment and seal around each tooth. This unique function imparts special challenges to the tissue and leads to certain vulnerabilities associated with periodontal disease, especially in view of the continual exposure to the bacterial biofilm (dental plaque) that forms on the tooth surface at the junction of the soft tissue. Thus, this anatomical region is one where there is a significant risk of bacterially induced infection and inflammation.Antimicrobial peptides are important contributors to maintaining the balance between health and disease in this complex environment. These include several salivary antimicrobial peptides, the β-defensins expressed in the epithelium, the α-defensins expressed in neutrophils, and the cathelicidin, LL-37, expressed in both epithelium and neutrophils. These peptides are part of the host innate immune response in this environment. Epithelia, polymorphonuclear leukocytes (neutrophils), and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. This review will focus on the human oral cavity and include 1) the expression and function of antimicrobial peptides in the oral cavity in the context of innate immune responses, 2) regulation of β-defensins which has led to advances in our understanding of oral epithelial innate immunity, and 3) functional efficacy against oral microbes when it is known. Epithelial antimicrobial peptidesHistorically, the oral epithelium has been considered mainly as a passive covering that becomes damaged and ulcerated in disease. This view has changed dramatically and the epithelial compartment is now seen as providing both...

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

“…It also allows reducing the dosages, attenuating side effects and enhancing selectivity of compounds (Chou, 2006). The concept of combined use comes even more naturally concerning the AMPs, as in many tissues these compounds are expressed together in certain groups and are shown to possess synergy with each other (Chen et al, 2005; Dale and Fredericks, 2005; Lai and Gallo, 2009; Marxer et al, 2016). Such synergy is believed to be one of the keys to their successfulness in combating different resistance mechanisms invented by pathogenic bacteria during the long evolutional coexistence with the immune system of the host (Guilhelmelli et al, 2013; LaRock and Nizet, 2015).…”

The multifaceted roles of antimicrobial peptides in oral diseases

“…Antimicrobial peptides play an essential role in innate immunity (Ganz, 2003) and help to prevent infections and maintain oral health. Research has focused on fostering an understanding of the involvement of antimicrobial peptides in mucosal disorders (Dale & Fredericks, 2005; Table 3).…”

Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview

“…Histatins are human oral anti-microbial peptides secreted by the salivary glands into the saliva and related to immunity [154]. The histatin family contains 12 small histidine-rich cationic AMPs with the most abundant ones being histatin 1, 3, and 5 [155].…”