A Cell Proliferation and Inflammatory Signature is Induced by Lawsonia intracellularis Infection in Swine

Abstract

11Lawsonia intracellularis causes porcine proliferative enteropathy. This is an enteric disease 12 characterized by thickening of the wall of the ileum that leads to decreased growth and diarrhea 13 of animals. In this study, we investigated the host response to L. intracellularis infection by

Oral Vaccination Reduces the Effects of Lawsonia intracellularis Challenge on the Swine Small and Large Intestine Microbiome

“…In the first description of PPE by Biester and Schwarte (23), it was noted that disease could be reproduced by feeding healthy swine intestinal contents and scrapings from affected pigs. Since then, gut homogenates, which comprise homogenate intestinal material from pigs with gross PPE lesions, have been described and used extensively to study L. intracellularis infection (4,20,24,25). In this study, we used shotgun metagenomic sequencing to investigate the bacterial and viral composition of L. intracellularis gut homogenate challenge material.…”

“…Fusobacterium and F. nucleatum abundance in colonic mucosa have been found to be significantly more abundant in patients with adenoma and colorectal cancer, and these bacteria have the capacity to induce severe TNF-mediated inflammation (31,32). Interestingly, gene expression pathways observed in intestinal tissue of pigs with PPE lesions have been found to be associated with a cellular proliferation and inflammatory signature resembling those of cancer and other inflammatory diseases of the intestinal tract (4,33). PPE of course is not a cancer, as lesions do resolve.…”

“…Similar to F. nucleatum, Bacteroides, and B. fragilis also have been implicated in colorectal cancer, in which certain strains have been found to be capable of promoting cellular proliferation by stimulation of Wnt signaling. The latter is a signaling pathway that has also been described to be altered in pigs with PPE (4,(34)(35)(36). Increased abundance of Bacteroides has also been found in the fecal microbiome of pigs challenged with a pure culture of L. intracellularis and to be negatively associated with weight gain in swine (8, 10).…”

“…L. intracellularis infects intestinal epithelial cells, preferentially those of the terminal ileum, and are present in cells in the crypts, causing hyperplasia leading to thickened intestinal tissue. Lesions in swine are also marked by a loss of mucin-producing goblet cells and a decrease of villus height (1,3,4). There are two clinical forms of PPE: porcine intestinal adenomatosis (PIA) and porcine hemorrhagic enteropathy (PHE).…”

Editorial: Lawsonia intracellularis: a problem well understood is a problem half solved

“…Notably, one of the plasmids (A) was entirely repressed in the non-pathogenic bacteria. Transcriptomic profiling of the host ileum tissue in L. intracellularis-infected pigs revealed the molecular signature of cellular proliferation and inflammation (11). The stimulation of Notch-1 signaling and inhibition of the β-catenin/Wnt pathway in ileum crypt cells during the peak of infection by L. intracellularis has been implicated in the molecular pathogenesis (12).…”