Campylobacter jejuniInduces Maturation and Cytokine Production in Human Dendritic Cells

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-B and significantly stimulated production of interleukin-1␤ (IL-1␤), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-␣) 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-1␤, IL-6, IL-8, and TNF-␣ and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.

TLR4-Mediated Sensing of Campylobacter jejuni by Dendritic Cells Is Determined by Sialylation

“…TLR4 engages LOS via lipid A, which leads to secretion of several inflammatory cytokines through activation of NF-kB transcription (20). Previous studies demonstrated NF-kB transcription in human DCs upon stimulation with C. jejuni LOS (26). Accordingly, the observed secretion of IL-12p40 and other cytokines induced by GBS-associated C. jejuni LOS in the current study was reduced when binding to TLR4 was prevented.…”

“…DCs reside directly under the epithelial cell layer; therefore, they are well positioned to interact with invasive and noninvasive pathogens (25). Previous studies showed that C. jejuni are readily internalized by DCs and induce cell maturation and cytokine production (26). In agreement with these findings in DCs, the current study demonstrated that LOS from GBS-related C. jejuni strains induced an upregulation of costimulatory cell surface markers, including CD40, CD80, CD86, and HLA-DR, and secretion of inflammatory cytokines, including IL-6, IL-8, IL-10, IL12p40, and TNF-a.…”

Virulence genes and cytokine profile in systemic murineCampylobacter coliinfection

“…43 Furthermore, the immune functions of cytokines result from the coordinated action of T cells, macrophages and dendritic cells, and these largely depend on the recruitment of these calls to the sites of infection and inflammation, and to other pathological lesions. 48 Previously, Hu et al (2006) 49 demonstrated that C. jejuni infection can trigger innate inflammatory responses, and induce human dendritic cell maturation and production of pro-inflammatory cytokines, including IL-6, IL-8, IL-12 and TNF-a. In this way, cytokines can induce Campylobacter-specific Th1 effector-cell responses, and contribute to the pathogenesis and clinical symptoms of Campylobacter spp.…”

“…[54][55][56] High levels of production of IL-12 initiate a Th1 polarized adaptive immune response. 49 Interleukin-10 functions as an anti-inflammatory cytokine, and it is known to suppress production of pro-inflammatory cytokines such as IL-12, TNF-a and IFN-g. In addition, its relationship with some pro-inflammatory cytokines is important for the outcome of infection and sepsis.…”

Participation of the Cytoskeletal and Lysosomal Compartments in Campylobacter jejuni Invasion of Caco-2 cells, the Cellular Response by Morphometric Analysis and the Presence of Cytokine and Chemokine Transcripts

“…We have not studied the levels of transcripts for IL-6 in a subsequent period however; others have found an increase in IL-6 in dendritic cells in late periods ([24 h) [11]. This may be explained by the early timing of the cell culture.…”