Investigation of the pathogenicity potential of Campylobacter concisus in oral inflammation

Abstract

Epidemiological studies showed that Campylobacter concisus, an emerging enteric pathogen, may also play a role in oral inflammatory diseases. However, limited studies have examined the oral pathogenicity of C. concisus. This thesis investigated the potential and pathogenic mechanisms of C. concisus in oral inflammation using human oral epithelial cell line H413 as a model. C. concisus upregulated the mRNA levels of IL-1b and IL-18 in H413 cells. Increased protein productions of IL-1b, TNF and IL-18, induced by C. concisus, in H413 cells were also detected. Further experiments confirmed that the strong IL-18 positive signal detected in the supernatant of C. concisus infected cells was bacterially derived. The effects of C. concisus strains on the gene expression of six tight junction proteins were examined. C. concisus infection upregulated claudin-1, claudin-4, claudin-8 and occludin expression in H413 cells, but not the expression of ZO-1 and JAM-1. Variations of C. concisus strains in the induction of proinflammatory cytokines and regulation of gene expression of tight junction proteins were observed. In conclusion, the findings that C. concisus upregulated the production of proinflammatory cytokines in oral epithelial cells support a role of C. concisus in oral inflammatory diseases. The finding that C. concisus released a molecule that was strongly cross-reactive to anti-human IL-18 monoclonal antibodies suggests that in future studies examining cytokines induced by bacterial microbes, a bacterium control should be included. Furthermore, upregulation of claudins by C. concisus suggests that this bacterium may facilitate the development of other diseases that are associated with increased claudin expression.