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The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells.

ABSTRACT: Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100) from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species.

SUBMITTER: John DA

PROVIDER: S-EPMC5626877 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells.

John Daniel A DA Williams Lisa K LK Kanamarlapudi Venkateswarlu V Humphrey Thomas J TJ Wilkinson Thomas S TS

Frontiers in microbiology 20170929

Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100) from multi-locus sequence typed collections to assess their pathogenic diversity, through t ...[more]

PMID: 29033908

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Project description:Campylobacter jejuni is a leading cause of bacterial foodborne illness in humans worldwide. However, C. jejuni naturally colonizes poultry without causing pathology where it resides deep within mucus of the cecal crypts. Mucus may modulate the pathogenicity of C. jejuni in a species-specific manner, where it is pathogenic in humans and asymptomatic in poultry. Little is known about how intestinal mucus from different host species affects C. jejuni gene expression. In this study we characterized the growth and transcriptome of C. jejuni NCTC11168 cultured in defined media supplemented with or without mucus isolated from avian (chicken or turkey) or mammalian (cow, pig, or sheep) sources. C. jejuni showed substantially improved growth over defined media, with mucus from all species, showing that intestinal mucus was an energy source for C. jejuni. Seventy-three genes were differentially expressed when C. jejuni was cultured in avian vs. mammalian mucus. Genes associated with iron acquisition and resistance to oxidative stress were significantly increased in avian mucus. Many of the differentially expressed genes were flanked by differentially expressed antisense RNA asRNA, suggesting a role in gene regulation. This study highlights the interactions between C. jejuni and host mucus and the impact on gene expression, growth and invasion of host cells, suggesting important responses to environmental cues that facilitate intestinal colonization. IMPORTANCE Campylobacter jejuni infection of humans is an important health problem world-wide and is the leading bacterial cause of foodborne illnesses in U.S. The main route for exposure for humans is consumption of poultry meat contaminated during processing. C. jejuni is frequently found in poultry, residing within the mucus of the intestinal tract without causing disease. It is not clear why C. jejuni causes disease in some animals and humans, while leaving birds without symptoms. To understand its activity in birds, we characterized C. jejuni responses to poultry mucus to identify genes turned on in the intestinal tract of birds. We identified genes important for colonization and persistence within the poultry gut, turned on when C. jejuni was exposed to poultry mucus. Our findings are an important step in understanding how C. jejuni responds and interacts in the poultry gut, and may identify ways to reduce C. jejuni in birds.

Dataset Information

The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells.

Publications

The Bacterial Species <i>Campylobacter jejuni</i> Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells.

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