Abstract
The epithelial barrier at mucosal sites comprises an important mechanical protective feature of innate immunity, and is intimately involved in communicating signals of infection/tissue damage to inflammatory and immune cells in these local environments. A wide array of antimicrobial factors (AMF) exist at mucosal sites and in secretions that contribute to this innate immunity. A non-human primate model of ligature-induced periodontitis was used to explore characteristics of the antimicrobial factor transcriptome (n = 114 genes) of gingival biopsies in health, initiation and progression of periodontal lesions, and in samples with clinical resolution. Age effects and relationship of AMF to the dominant members of the oral microbiome were also evaluated. AMF could be stratified into 4 groups with high (n = 22), intermediate (n = 29), low (n = 18) and very low (n = 45) expression in healthy adult tissues. A subset of AMF were altered in healthy young, adolescent and aged samples compared with adults (e.g., APP, CCL28, DEFB113, DEFB126, FLG2, PRH1) and were affected across multiple age groups. With disease, a greater number of the AMF genes were affected in the adult and aged samples with skewing toward decreased expression, for example WDC12, PGLYRP3, FLG2, DEFB128, and DEF4A/B, with multiple age groups. Few of the AMF genes showed a >2-fold increase with disease in any age group. Selected AMF exhibited significant positive correlations across the array of AMF that varied in health and disease. In contrast, a rather limited number of the AMF significantly correlated with members of the microbiome; most prominent in healthy samples. These correlated microbes were different in younger and older samples and differed in health, disease and resolution samples. The findings supported effects of age on the expression of AMF genes in healthy gingival tissues showing a relationship to members of the oral microbiome. Furthermore, a dynamic expression of AMF genes was related to the disease process and showed similarities across the age groups, except for low/very low expressed genes that were unaffected in young samples. Targeted assessment of AMF members from this large array may provide insight into differences in disease risk and biomolecules that provide some discernment of early transition to disease.
Highlights
The oral mucosa is a critical protective interface between external and internal environments and serves as a barrier to the myriad of microbial species in the oral microbiome
Determination of periodontal disease at the sampled site was documented by assessment of the presence of bleeding on probing (BOP) and probing pocket depth of >4 mm, as we have described previously [28]
APP, CCL28, DEFB113, DEFB126, FLG2, and PRH1 were differentially expressed in healthy gingival tissues across multiple age groups
Summary
The oral mucosa is a critical protective interface between external and internal environments and serves as a barrier to the myriad of microbial species in the oral microbiome. Due to the inherent structure where hard tissues (i.e., teeth) break through an intact epithelial barrier, this anatomical region is one where there is a significant risk of bacterially induced infection and inflammation To help manage this continual septic environment, a diverse family of antimicrobial factors is produced, which defend the oral cavity and other mucosal surfaces of the body. The innate immune system augmented the physical and chemical barriers by producing antimicrobial biomolecules (antimicrobial factors; AMF) with functionality against Gram-positive and negative bacteria, parasites, fungi, and viruses [1–3]. These factors, as a first line of defense, have multiple functions and properties that influence aspects of innate defenses and contribute to regulation of colonization by microorganisms
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