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.
Highlights
Campylobacter is a leading cause of bacterial food-borne diarrhoeal disease worldwide, with symptoms ranging from mild to serious infections, which can result in permanent neurological damage; especially in elderly people (Silva et al, 2011)
We investigated the response of 100 C. jejuni strains that have been characterized previously at the genome level (Sheppard et al, 2013) by investigating their inflammatory, adhesion, invasion, toxicity and signalling responses in 8E11 intestinal epithelial cells and compared these responses with human intestinal epithelial cells (HT-29)
We investigated the ability of high and low IL-8inducing C. jejuni strains (n = 35, final column Table 2) to adhere to and invade human and avian epithelial cells
Summary
Campylobacter is a leading cause of bacterial food-borne diarrhoeal disease worldwide, with symptoms ranging from mild to serious infections, which can result in permanent neurological damage; especially in elderly people (Silva et al, 2011). It is frequently found in poultry and chicken is an important source of Campylobacter infection. In the United Kingdom alone, Campylobacter is estimated to cause up to 700000 cases of infection and more than 100 deaths each year. Campylobacter infection costs the United Kingdom economy at least £900 million per year (DEFRA, 2012). Campylobacter jejuni is the most common species to cause a rare neuromuscular paralysis known as Guillain–Barré syndrome (Parkhill et al, 2000).
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