Campylobacter jejuni-Mediated Induction of CC and CXC Chemokines and Chemokine Receptors in Human Dendritic Cells

Hu, Lan; Bray, Mechelle D.; Yang, Geng; Kopecko, Dennis J.

doi:10.1128/iai.00129-12

Cited by 15 publications

(9 citation statements)

References 40 publications

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“…Our work contributes to recent contributions from large field trials, epidemiologic modeling studies, and experimental models [2,[16][17][18]. In addition to Campylobacter's known importance as a cause of symptomatic disease in children in resource-poor regions, the frequency of asymptomatic infection in all populations is becoming more recognized (Karen Kotloff [Global Enteric Multicenter Study] and William Petri Jr [Malnutrition and Enteric Diseases], personal communication) [1,2,19,20].…”

Section: Discussionmentioning

confidence: 93%

“…Human ex vivo intestinal epithelial and dendritic cell coculture systems show expansion of T helper 1 and T helper 17T cells after C. jejuni infection at the mucosal surface and suggest the importance of IFN-γ, interleukin 22, and the interleukin 17 family in the acute and effector phases of C. jejuni infection [18]. C. jejuni also induces dendritic cell maturity and induces proinflammatory cytokines and STAT3 activation [16,17]. Our observations from this human homologous rechallenge model caution that despite clinical and laboratory markers of inflammation, innate responses, and evidence of immunogenicity, clinical protection from disease (and corresponding adaptive immune responses) cannot be assumed to follow.…”

Section: Discussionmentioning

confidence: 99%

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Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model

Kirkpatrick

Lyon

Porter

et al. 2013

Clinical Infectious Diseases

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model

Kirkpatrick

Lyon

Porter

et al. 2013

Clinical Infectious Diseases

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“…Additionally, the mechanisms of epithelial cell invasion and intracellular survival are being elucidated, further suggesting that CD8 + T cell responses may be important in clearing infection [29] , [30] . While we investigated the CD8 + response and the chemokine MIP-1β, a chemokine important for recruitment of additional immune cells to sites on infection and produced by activated CD8 + and CD4 + cells, no clear patterns of CD8 + or MIP-1β responses were observed [31] – [33] .…”

Section: Discussionmentioning

confidence: 99%

Peripheral CD4+ T Cell Cytokine Responses Following Human Challenge and Re-Challenge with Campylobacter jejuni

et al. 2014

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Campylobacter jejuni is a leading cause of human gastroenteritis worldwide; however, our understanding of the human immune response to C. jejuni infection is limited. A previous human challenge model has shown that C. jejuni elicits IFNγ production by peripheral blood mononuclear cells, a response associated with protection from clinical disease following re-infection. In this study, we investigate T lymphocyte profiles associated with campylobacteriosis using specimens from a new human challenge model in which C. jejuni-naïve subjects were challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry was used to investigate T lymphocytes as a source of cytokines, including IFNγ, and to identify cytokine patterns associated with either campylobacteriosis or protection from disease. Unexpectedly, all but one subject evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+ T cells make IFNγ and other pro-inflammatory cytokines in response to infection; however, multifunctional cytokine response patterns were not found. Cytokine production from peripheral CD4+ T cells was not enhanced following re-challenge, which may suggest deletion or tolerance. Evaluation of alternative paradigms or models is needed to better understand the immune components of protection from campylobacteriosis.

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“…These receptors recognize microbial or danger-associated patterns and drive diverse sets of immune responses in a cell. Dendritic cells infected with C. jejuni induce the production of a range of cytokines, including tumor necrosis factor (TNF), gamma interferon (IFN-␥), interleukin 1␤ (IL-1␤), IL-8, IL-10, IL-12, and IL-23 (22)(23)(24). Evidence suggests that TLRs and NLRs, particular TLR2, TLR4, and NOD1, are important for driving proinflammatory cytokine production in response to C. jejuni infection (25,26).…”

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confidence: 99%

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus

et al. 2015

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e Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNAseq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA-and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-B, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus. Anumber of Campylobacter species, in addition to Campylobacter jejuni and Campylobacter coli, are now recognized as human and animal pathogens (1). Campylobacter concisus, first isolated from the oral cavity of humans in 1981 (2), is an emergent pathogen of the human gastrointestinal tract (3). C. concisus is a causative agent of a more prolonged but less severe form of acute gastroenteritis compared to that caused by C. jejuni (4-6). Infection with C. concisus can predispose individuals to the development of microscopic colitis and irritable bowel syndrome (6, 7). Furthermore, this bacterium has been associated with the development of more severe chronic conditions, such as inflammatory bowel diseases (IBD) (8-13) and Barrett's esophagus (14,15).Studies of C. concisus virulence factors have identified distinct pathogenic traits within different strains, which have been used to classify C. concisus strains into potential pathotypes, including adherent and invasive C. concisus (AICC) and adherent and toxigenic C. concisus (AToCC), in addition to nonpathogenic strains (16). The basis of this division arises from the ability of AICC to invade host cells and evade autophagy, thereby accumulating within host cells to intracellular levels 500-fold greater than those of other C. concisus strains (17-19), while AToCC strains produce a zonula occludens toxin with the potential to target tight junctions of host cells (20). A restriction-modification (R-M) system specific to AICC strains has been hypothesized to be involved in the ability of these strains to manipul...

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Campylobacter jejuni-Mediated Induction of CC and CXC Chemokines and Chemokine Receptors in Human Dendritic Cells

Abstract: ABSTRACTCampylobacter jejuniis a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms ofC. jejunipathogenesis have not been characterized in detail, host inflammato… Show more

Cited by 15 publications

References 40 publications

Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model

Lack of Homologous Protection Against Campylobacter jejuni CG8421 in a Human Challenge Model

Peripheral CD4+ T Cell Cytokine Responses Following Human Challenge and Re-Challenge with Campylobacter jejuni

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus

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