Darveau, Richard P.Chang, Ana Marie2019-08-142019-08-142019-08-142019Chang_washington_0250E_20378.pdfhttp://hdl.handle.net/1773/43965Thesis (Ph.D.)--University of Washington, 2019Over a half a century of research has identified that periodontitis is a result of dysbiosis of both the commensal microbial community as well as the host innate immune response. However, our lack of understanding oral health and how health is maintained has yet to produce a cure or sufficient treatment for this disease. The results from this investigation will bring novel insights into key innate host protective mechanisms which contribute to the maintenance of health. This work is a continuation of previous findings by Zenobia et al. which identified commensal bacteria directly contribute to neutrophil migration through select neutrophil chemotactic receptor, CXCR2, ligand expression and its expression is dependent on the MyD88 inflammatory pathway (Zenobia et al., 2013). Furthermore, Greer et al. identified that neutrophils along with the expression of its chemotactic molecule was not homogeneous within oral tissues, but rather displayed site-specific neutrophil migration and chemokine expression patterns (Greer et al., 2016). Chapter 2 identifies bacterial recognition receptors, toll-like receptors 2 (TLR2) and TLR4 , two upstream activators of the MyD88 activation pathway, which may be utilized by oral commensal bacteria in the selective expression of CXCR2 ligands and determines the role of these receptors in neutrophil recruitment, bacterial homeostasis, and alveolar bone loss. Chapter 3 addresses the role of a neutrophil activating receptor, CXCR1, in its role in oral homeostasis determined by its effect on neutrophil recruitment, microbial homeostasis and alveolar bone loss. Lastly, Chapter 4 identifies the immunomodulatory effects of a natural extract, Sud, against host and bacterially mediated production of a potent neutrophil chemoattractant, interleukin-8 (IL-8). These three chapters complement each other in that both oral commensal bacteria as well as cell intrinsic genetic regulatory mechanisms of inflammation exist to modulate health. This proposal will provide insights into the mechanisms of microbial- and host-mediated modulatory maintenance of healthy oral homeostasis, and hence a better understanding for the prevention of dysbiosis.application/pdfen-USCC BYCXCR1Junctional EpitheliumNeutrophilsOral HealthPlant ExtractToll-like ReceptorHealth sciencesDentistryThesis