Abstract
Enterotoxigenic Escherichia coli (ETEC) is an important cause of post-weaning diarrhea (PWD) worldwide, resulting in huge economic losses to the swine industry worldwide. In this study, to understand the pathogenesis, the transcriptomic analysis was performed to explore the biological processes (BP) in porcine intestinal epithelial J2 cells infected with an emerging ETEC strain isolated from weaned pigs with diarrhea. Under the criteria of |fold change| (FC) ≥ 2 and P < 0.05 with false discovery rate < 0.05, a total of 131 referenced and 19 novel differentially expressed genes (DEGs) were identified after ETEC infection, including 96 upregulated DEGs and 54 downregulated DEGs. The Gene Ontology (GO) analysis of DEGs showed that ETEC evoked BP specifically involved in response to lipopolysaccharide (LPS) and negative regulation of intracellular signal transduction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response-related pathways were mainly enriched in J2 cells after ETEC infection, in which tumor necrosis factor (TNF), interleukin 17, and mitogen-activated protein kinase (MAPK) signaling pathways possessed the highest rich factor, followed by nucleotide-binding and oligomerization domain-like receptor (NLRs), C-type lectin receptor (CLR), cytokine–cytokine receptor interaction, and Toll-like receptor (TLR), and nuclear factor kappa-B (NF-κB) signaling pathways. Furthermore, 30 of 131 referenced DEGs, especially the nuclear transcription factor AP-1 and NF-κB, participate in the immune response to infection through an integral signal cascade and can be target molecules for prevention and control of enteric ETEC infection by probiotic Lactobacillus reuteri. Our data provide a comprehensive insight into the immune response of porcine intestinal epithelial cells (IECs) to ETEC infection and advance the identification of targets for prevention and control of ETEC-related PWD.
Highlights
Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in animals and humans
The criteria set of P-value and FC significantly affects the number of differentially expressed genes (DEGs) and results of functional and pathway enrichment analysis
A previous study showed that 2,443 DEGs were found in J2 cells infected F4ab ETEC with under the criteria of |FC| > 1.5 and P < 0.05 with FDR < 0.252, whereas only 1,188 DEGs were found under the criteria of |FC| > 2 and P < 0.05 [9]
Summary
Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in animals and humans. The breakout of ETEC infection in farm animals often attracts a lot of attention due to the possibility of spreading to humans through animal productions. Enterotoxigenic Escherichia coli-expressing F4 fimbriae are the most prevalent strains in pigs [4] and include three fimbrial variants of F4ab, F4ac, and F4ad [5]. F4ab and F4ac variants are typically associated with diarrhea in pigs [6]. The incidence of ETEC infection has become a more frequent reason for severe diarrhea in global swine production. Across Europe, ETEC is detected in 60% of post-weaning diarrhea (PWD)-affected farms [7]. Enterotoxigenic Escherichia coli is responsible for the spread of antibiotic resistance in the environment [8]. Clarifying the pathogenesis of ETEC is essential for identifying effective prevention strategies for ETEC-related pig diarrhea
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