The contribution of oral commensal bacteria to oral health is not fully understood. In contrast, intestinal commensal bacteria have been shown to contribute to intestinal protection mechanisms though interactions with the host's innate and adaptive immune systems. The oral and intestinal environments are similar in that they both carry a heavy microbial burden and are located next to host tissues which need to remain sterile to be fully functioning and healthy. Specifically, the periodontium is highly vascularized providin a means by which bacteria or their components can enter the bloodstream and potentially contribute to systemic disease. Accordingly, studies have demonstrated that periodontal tissue in both humans and rodents contain an unusual constant heavy flow of neutrophils from the highly vascularized periodontal tissue to the gingival crevice where they serve as a major host protection mechanism. However, little is known how periodontal tissue orchestrates this constant inflammatory surveillance mechanism. In this proposal our overall hypothesis is that oral commensal bacteria contribute to innate defense homeostasis by the selective expression of neutrophil chemokine receptor CXCR2 ligands. This hypothesis will be examined by studies defining chemokine ligand expression in germ free and conventionally reared mice (Specific Aim 1), determining the contribution of select oral bacteria to chemokine ligand expression (Specific aim 2), and elucidating host activation mechanisms with the use of select knockout mice (Specific aim 3). These studies will lay a foundation for understanding this key periodontal host protection mechanism which can then be used to develop novel intervention and preventative therapies.
This application will determine how the commensal bacteria that live in our mouths, specifically next to our teeth may help our tissue protect itself from pathogenic bacteria. Understanding the contribution of potentially beneficial bacteria will aid in the development of new preventative and therapeutic interventions for periodontitis.
| Greer, A; Irie, K; Hashim, A et al. (2016) Site-Specific Neutrophil Migration and CXCL2 Expression in Periodontal Tissue. J Dent Res 95:946-52 |
