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

Abstract

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-α. 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.

A bovine lactoferricin-lactoferrampin-encoding Lactobacillus reuteri CO21 regulates the intestinal mucosal immunity and enhances the protection of piglets against enterotoxigenic Escherichia coli K88 challenge

“…The degradation of the intestinal barrier can provide a beneficial environment for the proliferation of the pathogen and potentiate more severe disease symptoms. 51 The function of the intestinal barrier is related to many factors, including D-lactate, endotoxins in serum, and intestinal epithelial tight junction (TJ) proteins. 52,53 Elevated levels of D-lactate in serum are usually accompanied by impaired function of the intestinal barrier.…”

The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

“…Compared to infection with the C. jejuni wild-type strain, mice infected with the ciaD deletion mutant have reduced GI tract wall thickening and reduced inflammation of the ileocecocolic lymph node 23 . More recently, the application of a pig ligated loop model also revealed that a C. jejuni ∆ciaD mutant does not induce the characteristic robust inflammatory response observed with a C. jejuni wild-type strain, as demonstrated by the production of inflammatory cytokines and neutrophil markers 30 . Laboratory studies have shown that CiaD is mechanistically involved in host cell uptake of C. jejuni by promoting actin reorganization and membrane ruffling via Erk 1/2 activation 28 .…”

Multi-Omics Approach Reveals the Potential Core Vaccine Targets for the Emerging Foodborne Pathogen Campylobacter jejuni

“…In order to gain further insights into the responses of the potential core vaccine candidates and core VFs to different stresses, we selected two transcriptome data to analyze the gene expression in different experiments of human and pig ( Negretti et al, 2019 , 2020 ). In the environment of co-culturing with human INT 407 and Caco-2 cells, the expression levels of 126 genes, including the 25 core VFs (which include sodB , cadF , and flgC ) that were found in this study, were increased and the expression levels of 148 genes (including 13 core VFs) were decreased under human immune stress ( Figures 4A,B ).…”

“…These results indicate that the flagellar genes are important VFs, which are essential for C. jejuni motility and the secretion of virulence proteins. The differences in the gene expressions could be caused by the different transcriptional responses by different hosts or the need for a certain reaction time after infection ( Negretti et al, 2020 ). In this study, transcriptome analysis of C. jejuni indicated that the core VFs play important roles under different stresses.…”