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The Role of Fusobacterium nucleatum in Canonical Inflammasome Activation in Gingival Epithelial Cells

  • Author(s): Bui, Fiona Quyen
  • Advisor(s): Chin, Wei-Chun
  • et al.
Abstract

Fusobacterium nucleatum is an invasive anaerobic bacterium, which is ubiquitous in human dental plaque and is frequently associated with periodontal diseases. Previous studies have focused on the virulence factors produced during infection of F. nucleatum and disease progression, but early recognition by the immune system and the role of the inflammasome in response to bacteria is not well characterized. Furthermore, although an inflammasome in gingival epithelial cells (GECs) can be stimulated by danger-associated molecular pattern molecules (DAMPs) such as ATP, inflammasome activation by this periodontal pathogen has yet to be described in these cells. We aimed to examine the effects of F. nucleatum infection on pro-inflammatory cytokine expression and inflammasome activation in GECs. Our results indicate that infection induces translocation of NF-κB into the nucleus, resulting in cytokine gene expression. In addition, infection activates the NLRP3 inflammasome, which in turn activates caspase-1 and release of mature IL-1β. Unlike other pathogens studied until now, F. nucleatum activates the inflammasome in GECs in the absence of exogenous DAMPs. Finally, infection promotes release of other DAMPs mediating inflammation, such as high-mobility group protein B1 (HMGB1) and apoptosis-associated speck-like protein, with a similar time-course as caspase-1 activation. Thus, F. nucleatum expresses the pathogen-associated molecular patterns (PAMP) necessary to activate NF- κB, and also provides an endogenous DAMP to stimulate the inflammasome and further amplify inflammation through secretion of secondary DAMPs. Our findings can provide novel pathway of F. nucleatum invasion and improve our understanding of its roles in periodontal infection. Thus, research on pathogenic mechanisms and the hosts’ immune system can postulate the relationship between oral pathogens and emerging systemic diseases.

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