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

Abstract

Lawsonia intracellularis is among the most important enteric pathogens of swine, and it can also infect other mammalian species. Much is still unknown regarding its pathogenesis and the host response, especially at the site of infection. In this study, we uncovered several novel genes and pathways associated with infection. Differentially expressed transcripts, in addition to histological changes in infected tissue, revealed striking similarities between L. intracellularis infection and cellular proliferation mechanisms described in some cancers and inflammatory diseases of the gastrointestinal tract. This research sheds important light into the pathogenesis of L. intracellularis and the host response associated with the lesions caused by infection.

Lawsonia intracellularis infected enterocytes lack sucrase-isomaltase which contributes to reduced pig digestive capacity

“…Thus, it is likely a greater number of macrophages present in PC pig ileal tissue led to the greater mitochondrial ROS production rates reported herein. Consistent with this postulation, previous work has found increased abundance of xanthine dehydrogenase in L. intracellularis challenged pigs, an enzyme which regulates production of ROS and nitric oxide synthase to control bacterial infections [ 26 ].…”

“…Gene abundance studies [ 8 , 9 , 26 ] have observed mRNA transcript changes to pathways involved in cellular transport, inflammation, and mucus production during peak infection which would suggest L. intracellularis reduces nutrient digestion, nutrient transport, and mucosal integrity. Further, the pathogen is purported to induce inflammatory and cell proliferation pathways associated with disease [ 26 ]. However, the functional implications this pathogen and its associated disease has on digestibility and intestinal permeability are largely unknown.…”

“…In addition to production by macrophages, IL-1β production by infected enterocytes is critical in the formation of the inflammasome, a key component of controlling and clearing intracellular pathogens [ 47 , 48 ]. However, excessive production of this cytokine could be responsible for a number of effects of pig metabolism, including reduced feed intake [ 49 ], impaired nutrient transporter function [ 50 ], or even hyperplasia of intestinal enterocytes [ 26 , 51 ]. The vaccinated pigs had lesser evidence of inflammation, as many proinflammatory cytokine concentrations were equivalent to that of the NC control pigs, which likely contributed to their greater performance and health during pathogen challenge.…”

“…Contradictory to our data herein, these researchers also observed a concurrent reduction in WNT3A transcript abundance and postulated that L. intracellularis may downregulate β-catenin/Wnt signaling at the peak of infection [ 35 ]. However, Leite et al [ 26 ] did observe activation of the Wnt/Ca + pathway in L. intracellularis challenged pigs. Disparities in WNT3A transcript abundance between these studies may be due to differences in disease severity and progression.…”

Histopathological changes in pigs infected with ileitis

“…The disease occurs in four different forms, namely: regional ileitis, intestinal adenomatosis, hemorrhagic enteropathy, necrotic enteritis. It is characterized by intestinal disorders and progressive weight loss in pigs (Lawson et al, 2000;McOrist et al, 2006;Karuppannan & Opriessnig, 2018;Leite et al, 2019). In general, Ileitis has a negative effect on pork's production, by reducing the average daily weight gain, feeding efficiency and deteriorating of the intestines function of the animals (Kukushkin et al, 2012;Jacobset al, 2019;.…”