Host defense peptides in the oral cavity and the lung: similarities and differences

Abstract

Peptides with broad-spectrum antimicrobial activity are found in the mucosal surfaces at many sites in the body, including the airway, the oral cavity, and the digestive tract. Based on their in vitro antimicrobial and other immunomodulatory activities, these host defense peptides have been proposed to play an important role in the innate defense against pathogenic microbial colonization. The genes that encode these peptides are up-regulated by pathogens, further supporting their role in innate immune defense. However, the differences in the local microbial environments between the generally sterile airway and the highly colonized oral cavity suggest a more complex role for these peptides in innate immunity. For example, beta-defensin genes are induced in the airway by all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-kappaB-mediated pathway. In contrast, the same genes are induced in the gingival epithelium by only a subset of bacteria and TLR ligands, via different pathways. Furthermore, the environments into which the peptides are secreted--specifically saliva, gingival crevicular fluid, and airway surface fluid--differ greatly and can effect their respective activities in host defense. In this review, we examine the differences and similarities between host defense peptides in the oral cavity and the airway, to gain a better understanding of their contributions to immunity.

Figure 1

ClustalW alignment of human α- and β-defensins. The mature peptide sequences of α- and β-defensins are aligned with the number of amino acids listed on the right. Amino acids are annotated based on the ClustalW scheme for physical characteristics: uppercase for small and hydrophobic, italic for acidic, boldface for basic, and underlined for hydroxyl, amide, and basic. Highly conserved residues in each sequence are denoted by an asterisk.

Figure 2

Pathways stimulated by microbes and their associated molecular patterns in oral (A) and airway (B) epithelial cells leading to β-defensin expression. These models are based solely on published studies demonstrating the role of the respective receptors, adapter molecules, and transcription factors. In some cases, e.g., stimulation of hBD-2 by P. intermedia, specific stimulatory molecule, receptor, pathway, and/or transcription factors have not been identified, and are shown as a question mark.