Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni

Journal Article · · Gut Microbes
The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen’s virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-a. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ?ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.
Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1924514
Report Number(s):
PNNL-SA-166370
Journal Information:
Gut Microbes, Journal Name: Gut Microbes Journal Issue: 1 Vol. 12
Country of Publication:
United States
Language:
English

References (78)

Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin journal January 2012
Avian Intestinal Mucus Modulates Campylobacter jejuni Gene Expression in a Host-Specific Manner journal January 2019
Structural Characterization of Campylobacter jejuni Lipooligosaccharide Outer Cores Associated with Guillain-Barré and Miller Fisher Syndromes journal January 2007
Characterization of the oxidative stress stimulon and PerR regulon of Campylobacter jejuni journal January 2009
MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses journal May 2016
Campylobacter Enteritis: Clinical and Epidemiologic Features journal August 1979
Regulation of Intestinal -Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense journal October 1999
Protective and pathogenic functions of macrophage subsets journal October 2011
How Intestinal Bacteria Cause Disease journal March 1999
Molecular Dissection of the Campylobacter jejuni CadF and FlpA Virulence Proteins in Binding to Host Cell Fibronectin journal March 2020
Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization: Flagellar coexpressed determinants of C. jejuni journal March 2012
g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) journal May 2019
Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion journal March 2003
The SILVA ribosomal RNA gene database project: improved data processing and web-based tools journal November 2012
Human S100A9 potentiates IL-8 production in response to GM-CSF or fMLP via activation of a different set of transcription factors in neutrophils journal May 2014
The Perseus computational platform for comprehensive analysis of (prote)omics data journal June 2016
Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry journal November 2006
Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures journal July 2000
The Complete Campylobacter jejuni Transcriptome during Colonization of a Natural Host Determined by RNAseq journal August 2013
Biochemical characterization of the neutrophil-specific antigen NB1 journal February 1990
Lipooligosaccharide locus class of Campylobacter jejuni: sialylation is not needed for invasive infection journal June 2014
Campylobacter colitis: histological immunohistochemical and ultrastructural findings. journal September 1985
Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. journal February 1989
DADA2: High-resolution sample inference from Illumina amplicon data journal May 2016
The MaxQuant computational platform for mass spectrometry-based shotgun proteomics journal October 2016
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy journal June 2007
A direct-sensing galactose chemoreceptor recently evolved in invasive strains of Campylobacter jejuni journal October 2016
Integrin activation by the lipid molecule 25-hydroxycholesterol induces a proinflammatory response journal April 2019
Translocation of Campylobacter jejuni across Human Polarized Epithelial Cell Monolayer Cultures journal August 1992
Campylobacter jejuni outer membrane vesicle-associated proteolytic activity promotes bacterial invasion by mediating cleavage of intestinal epithelial cell E-cadherin and occludin : Campylobacter jejuni OMV-associated proteolytic activity journal November 2015
Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni journal October 2007
Campylobacter jejuni Colonization of Mice with Limited Enteric Flora journal September 2006
The Campylobacter jejuni CiaC virulence protein is secreted from the flagellum and delivered to the cytosol of host cells journal January 2012
Cutting Edge: Bacterial Flagellin Activates Basolaterally Expressed TLR5 to Induce Epithelial Proinflammatory Gene Expression journal August 2001
Chemotactic behavior of Campylobacter jejuni. journal January 1988
Campylobacter jejuni-Stimulated Secretion of Interleukin-8 by INT407 Cells journal January 1999
Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine journal October 2005
Intestinal Epithelium-Specific MyD88 Signaling Impacts Host Susceptibility to Infectious Colitis by Promoting Protective Goblet Cell and Antimicrobial Responses journal June 2014
A re-examination of the role of Campylobacter fetus subspecies coli in enteric disease of the pig journal August 1981
Peripheral CD4+ T Cell Cytokine Responses Following Human Challenge and Re-Challenge with Campylobacter jejuni journal November 2014
Campylobacter jejuni Infection in Broiler Chickens journal March 2006
Myeloperoxidase: a front-line defender against phagocytosed microorganisms journal October 2012
The Host Antimicrobial Protein Calgranulin C Participates in the Control of Campylobacter jejuni Growth via Zinc Sequestration journal April 2018
Quantifying and Understanding Well-to-Well Contamination in Microbiome Research journal June 2019
Characterization and remediation of sample index swaps by non-redundant dual indexing on massively parallel sequencing platforms journal May 2018
Attachment, Invasion, and Translocation of Campylobacter jejuni in Pig Small-Intestinal Epithelial Cells journal May 2010
Pseudaminic Acid on Campylobacter jejuni Flagella Modulates Dendritic Cell IL-10 Expression via Siglec-10 Receptor: A Novel Flagellin-Host Interaction journal May 2014
Blockade of Antimicrobial Proteins S100A8 and S100A9 Inhibits Phagocyte Migration to the Alveoli in Streptococcal Pneumonia journal February 2008
Identification of a Campylobacter jejuni -secreted protein required for maximal invasion of host cells journal August 2009
Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. journal January 1993
Evaluation of Agar Plates for Direct Enumeration of Campylobacter spp. from Poultry Carcass Rinses journal June 2005
Central role of IL-17/Th17 immune responses and the gut microbiota in the pathogenesis of intestinal fibrosis journal January 2014
Newborn piglet model for campylobacteriosis. journal January 1993
The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species journal November 2017
The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease journal January 2013
Campylobacter jejuni Infections: Update on Emerging Issues and Trends journal April 2001
In-feed bacitracin methylene disalicylate modulates the turkey microbiota and metabolome in a dose-dependent manner journal June 2019
Identification of a fibronectin-binding domain within the Campylobacter jejuni CadF protein: C. jejuni fibronectin-binding protein journal July 2005
The Reactome Pathway Knowledgebase journal November 2017
Human Intestinal Barrier Function in Health and Disease journal January 2016
Campylobacter jejuni FlpA Binds Fibronectin and Is Required for Maximal Host Cell Adherence journal October 2009
Campylobacter jejuni enters gut epithelial cells and impairs intestinal barrier function through cleavage of occludin by serine protease HtrA journal February 2019
Absorption of bile salts from the small intestine in vivo journal January 1962
Reconstitution of a Functional Toll-like Receptor 5 Binding Site in Campylobacter jejuni Flagellin journal February 2010
The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response journal December 2012
Mucosal Lipocalin 2 Has Pro-Inflammatory and Iron-Sequestering Effects in Response to Bacterial Enterobactin journal October 2009
Innate immunity in the small intestine journal January 2011
MRP-8 and MRP-14, two abundant Ca 2+ -binding proteins of neutrophils and monocytes journal February 1993
Experimental Campylobacter jejuni Infection in Humans journal March 1988
Increased expression of surface activation markers on neutrophils following migration into the nasal lumen journal August 2003
The role of neutrophils in the event of intestinal inflammation journal December 2009
Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides journal December 1997
Acute diarrhoea: Campylobacter colitis and the role of rectal biopsy. journal October 1979
The Intestinal Microbiota Influences Campylobacter jejuni Colonization and Extraintestinal Dissemination in Mice journal May 2015
The focal complex of epithelial cells provides a signalling platform for interleukin-8 induction in response to bacterial pathogens: Pathogen-mediated IL-8 induction journal June 2014
Fibronectin-Facilitated Invasion of T84 Eukaryotic Cells by Campylobacter jejuni Occurs Preferentially at the Basolateral Cell Surface journal December 2002
Serine phosphorylation of cortactin is required for maximal host cell invasion by Campylobacter jejuni journal January 2013
CheY‐mediated modulation of Campylobacter jejuni virulence journal March 1997

Similar Records

A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni
Journal Article · Thu Sep 03 20:00:00 EDT 2020 · Gut Microbes · OSTI ID:1671036