Endotoxin tolerance as a novel regulatory mechanism of the oral mucosal innate immune response during chronic periodontitis

The overall objective of the thesis is to establish how specific myeloid components of the human oral mucosa recognize and respond to microbial stimuli in the oral environment. These studies have now yielded what is believed to be novel and unexpected findings with a potential for enormous future research. These results shed particular light on how the innate response in oral mucosa, when faced with enormous microbial burden, attempts to curtail inflammatory response and attain tissue homeostasis, but may ultimately compromise the development of adaptive immunity and of local bone metabolism.; The overall aims of the thesis were: (I) To determine in human subjects the expression and transcriptional regulation of the Toll-like receptors (TLRs) in the gingival epithelium and lamina propria during gingival health and chronic periodontitis (CP) in situ; (II) To establish, using in vitro human monocyte and macrophage cultures, the roles of TLRs in induction of genes and proteins involved in innate and adaptive immune responses to microbial agonists.; The research conducted towards the Ph.D. thesis has provided novel evidence that a strategy for immunoregulation of the oral mucosal innate immune response involves induction of endotoxin tolerance during chronic inflammatory conditions like chronic periodontitis. Endotoxin tolerance may thus be a protective mechanism for the host to attempt to reestablish tissue homeostasis during chronic periodontitis. Despite efforts by the host to down modulate the inflammatory response by induction of endotoxin tolerance, the development of (protective) adaptive immune response may be compromised and hard tissue homeostasis may also be disrupted. (Abstract shortened by UMI.)...