Abstract
Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that Stx potently remodels the host innate immune response to EHEC.
Highlights
Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen responsible for up to 2 million annual cases of acute gastrointestinal illness [1]
Comparisons of the transcriptional responses to infection by strains containing or lacking Shiga toxins (Stx) revealed that this toxin markedly remodels how the epithelial cell compartment responds to infection
Our findings suggest that Stx shapes the intestinal innate immune response to EHEC and provide insight into the complex host-pathogen dialogue that underlies disease
Summary
Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen responsible for up to 2 million annual cases of acute gastrointestinal illness [1]. EHEC typically leads to self-limited hemorrhagic colitis; 5–10% of infected individuals develop hemolytic uremic syndrome (HUS), a potentially life-threatening complication that can lead to renal failure [2,3]. Supportive rehydration therapy remains the primary treatment for EHEC infection, as antibiotics are associated with elevated frequencies of HUS and contraindicated [4]. EHEC infection is associated with an inflammatory response in the colon, and patients have elevated fecal leukocytes and calprotectin levels. Colonic biopsy samples from patients with EHEC infection exhibit inflammation, edema, fibrin deposition, neutrophil invasion, and hemorrhage [5,6,7,8,9]
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