Hu L, Bray MD, Osorio M, Kopecko DJ. Campylobacter jejuni induces maturation and cytokine production in human dendritic cells

Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, NIH Campus, Bethesda, MD 20892, USA.
Infection and Immunity (Impact Factor: 3.73). 06/2006; 74(5):2697-705. DOI: 10.1128/IAI.74.5.2697-2705.2006
Source: PubMed


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.

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Available from: Lan Hu, Jul 17, 2014
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    • "Infection of mice followed by systemic C. jejuni spread and the infection of internal organs has indicated that the mouse is a useful in vivo model to demonstrate bacterial dissemination and tissue invasion (Vu ckovicét al., 1998). A significant part of C. jejuni pathogenesis is connected with the effects of lipopolysaccharides, which are responsible for the production of several cytokines (Hu et al., 2006). "
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    ABSTRACT: Abstract Campylobacters have developed a number of mechanisms for responding to environmental conditions, although the different virulence properties of these cells following exposure to stress are still poorly understood. We analyzed in vitro stress responses and the consequent in vivo modulation of Campylobacter jejuni pathogenicity in BALB/c mice, as a result of the exposure of the C. jejuni to environmental stress (starvation, oxidative stress, heat shock). In vitro, the influence of starvation and oxidative stress was milder than that of heat shock, although the majority of the stress conditions influenced the survival of C. jejuni. During starvation, C. jejuni viability was maintained longer than its culturability. Additionally, starvation elicited transformation of stressed bacteria to coccoid forms. In contrast, bacteria exposed to oxygen remained culturable, but their viability decreased. Pre-starvation did not contribute to improved survival of C. jejuni cells during oxygen exposure. Changes in bacteria numbers and the levels of several cytokines (interleukins 6 and 10, tumor necrosis factor-α, interferon-γ) were followed in vivo, in liver homogenates from the mice intravenously infected with either control (untreated) or stressed C. jejuni. The systemic infection with the control or stressed C. jejuni occurred with different production dynamics of the cytokines investigated. Starvation was the most powerful stress factor, which significantly decreased infectious potential of C. jejuni during the first 3 days postinfection. The most pronounced differences in cytokine production were found in interferon-γ and interleukin-10 production, which indicates that these have roles in the immune response to C. jejuni infection. These in vivo studies of environmental impact on bacterial virulence reveal that microbial adaptation during stress challenge is crucial not just for pathogen survival out of the host, but also during host-pathogen interactions, and thus for the bacterial pathogenicity.
    Foodborne Pathogens and Disease 05/2013; 10(6). DOI:10.1089/fpd.2012.1298 · 1.91 Impact Factor
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    • "C. jejuni invades epithelial cells in vitro [3], and can be isolated from the spleen and liver in infected animals [4,5]. In vitro studies demonstrated the production of proinflammatory cytokines in C. jejuni-infected monocytic [6], dendritic [7] and intestinal epithelial cell lines [8], peripheral blood mononuclear cells [9] and splenocytes [10]. The association between cytokine production and disease protection/resolution, suggested in patients [9], was shown by the increased susceptibility of mice deficient in MyD88 or NF-κB to C. jejuni[11,12]. "
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    ABSTRACT: Background Cytokine production and histopathological changes occur in the lungs of mice after intranasal inoculation with Campylobacter jejuni, but the levels of cytokines in different organs to which C. jejuni disseminates have not been studied. Findings Adult BALB/c mice were intranasally inoculated with C. jejuni 81–176 (test) or phosphate-buffered saline (control) (n=16 per group). The levels of cytokines in the organs (spleen, liver, and small and large intestines) to which C. jejuni disseminated were measured by ELISA. Two cytokine patterns were observed. First, increased proinflammatory cytokines, TNF-α, IL-1, and IL-2, were followed by anti-inflammatory cytokines, IL-4 and IL-10 in the spleen and large intestine. Second, in the liver and small intestine, there was a predominant production of anti-inflammatory cytokines, IL-4 and IL-10, with some increase in IL-2 levels. In the spleen and intestines, the levels of pro- and anti-inflammatory cytokines were concurrently increased. Conclusion Dissemination of C. jejuni is associated with the production of different cytokine profiles in different tissues, with the proinflammatory response appearing in the spleen and large intestine at an earlier time point than in the liver and small intestine. The organs produce different cytokine profiles in response to C. jejuni dissemination. These preliminary findings should be confirmed with a study involving a larger group of animals.
    Gut Pathogens 12/2012; 4(1):23. DOI:10.1186/1757-4749-4-23 · 2.28 Impact Factor
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    • "In previous studies, infections of dendritic cells with Campylobacter jejuni (Hu et al., 2006), Salmonella enterica serovar Typhimurium (Norimatsu et al., 2004), and Helicobacter pylori (Kranzer et al., 2004) have been shown to up regulate dendritic cell surface expression of MHC II, CD40, CD80, and CD86 molecules. We observed a consistent increase in CD80 and CD86 expression in biofilm mode E. faecalis-infected dendritic cells and macrophages when MFI or percent number of cells were compared. "
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    ABSTRACT: Enterococcus faecalis is a commensal organism of the gastrointestinal tract but can also cause serious opportunistic infections. In addition to high levels of antibiotic resistance, the ability to form biofilms on abiotic surfaces and on in-dwelling devices within the host complicates treatment strategies and successful outcomes of antibiotic therapy. Despite rapid advances made in recent years in understanding the genomics and virulence of this organism, much remains to be learned regarding the host response to enterococcal infections. In this study, we investigated the interaction of RAW264.7 macrophages and JAWS II dendritic cells with biofilm and planktonic E. faecalis, in vitro. Specifically, we compared phagocytosis, intracellular survival, secretion of proinflammatory cytokines, and the activation and maturation of phagocytes. Our results revealed that both macrophages and dendritic cells phagocytize biofilm mode cells at levels equal to or better than their planktonic counterparts. Internalized biofilm bacteria showed relatively greater survival at 24 h in macrophages than in dendritic cells and led to slightly higher expression of phagocyte activation markers. Macrophages infected with biofilm cells also secreted lower levels of proinflammatory cytokines studied. Overall, these results suggest that biofilm E. faecalis may be better adapted to overcome host defenses in vivo.
    FEMS Immunology & Medical Microbiology 02/2012; 65(2):270-82. DOI:10.1111/j.1574-695X.2012.00944.x · 3.08 Impact Factor
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