Campylobacter jejuniInduces Maturation and Cytokine Production in Human Dendritic Cells

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Abstract
Campylobacter jejuniis a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells andC. jejuniwas studied. We found thatC. jejuniwas readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) withC. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity ofC. jejunito dendritic cells was observed.C. jejuniinduced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition,Campylobacter-infected DCs triggered activation of NF-κB and significantly stimulated production of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-α) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killedC. jejunistimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide ofC. jejuniappears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection,Campylobactertriggers an innate inflammatory response through increased production of IL-1β, IL-6, IL-8, and TNF-α and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.

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