Affiliation:
1. Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, NIH Campus, Building 29/420, HFM440, Bethesda, Maryland 20892
Abstract
ABSTRACT
Campylobacter jejuni
is 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 and
C. jejuni
was studied. We found that
C. jejuni
was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with
C. jejuni
, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of
C. jejuni
to dendritic cells was observed.
C. jejuni
induced 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-killed
C. jejuni
stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of
C. jejuni
appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection,
Campylobacter
triggers 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
84 articles.
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