Down-regulation of mechanisms involved in cell transport and maintenance of mucosal integrity in pigs infected with Lawsonia intracellularis

Abstract

Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated transcripts, CD163 and CDK1 were novel findings and considered to be important, due to their respective roles in innate immunity and cellular proliferation. Overall, targeted cellular mechanisms included those that are important in epithelial restitution, migration and protection; maintenance of stable inter-epithelial cell relationships; cell transport of nutrients and electrolytes; innate immunity; and cell cycle.

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

“…In this study, at 14 dpi the lack of differentially expressed genes coincided with low lesion severity and antigen load. This was also observed by Smith et al 2014 who analyzed L. intracellularis infected intestine tissue samples at different time points by microarray analysis and found that the number of DEG coincided with the quantity of L. intracellularis present in tissue. This indicates there isn’t a robust host response during early stages of the infection and this coincides with lower lesions.…”

“…Elevated levels of TNF-α and TGF-β have been found in the infected intestinal mucosa (4, 5) along with an antigen-specific IgA response (6). Infiltration of inflammatory cells, particularly neutrophils, is not a primary feature of infection (1), although accumulation of macrophages has been found to coincide with increased lesion severity and antigen load in this disease (7, 8).…”

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

“…Other genes found in the present research and related to inflammatory conditions of the adipose tissue in FAT pigs are particularly interesting to mention: CD163, a member of the scavenger receptor cysteine-rich superfamily (Guo et al 2014;Smith et al 2014); solute carrier family 11 (protoncoupled divalent metal ion transporter), member 1 (SLC11A1), a gene involved in resistance to Salmonella infection (Kommadath et al 2014); chemokine (C-C motif) receptor 1 (CCR1), which was previously found to be overexpressed in obese pigs (Kogelman et al 2014); BCL2-related protein A1 (BCL2A1), a gene found to be overexpressed in pigs with a high obesity index and that is related to immunity, inflammatory pathways and osteoclast differentiation (Kogelman et al 2014); and CD1a molecule (CD1A; indicated as PCD1A in the cited paper), a surface antigen involved in immunity that was found to be overexpressed in obese pigs by Kogelman et al (2014). The same authors highlighted a strong connection between fat deposition on the body (obesity), immunity and bone development.…”

Lawsonia intracellularis exploits β-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation

“…intracellularis infection is associated with the loss of matured goblet cells [4]. Loss of secretory goblet cells and absorptive enterocytes causes disruption to the mucosal integrity and reduced uptake of nutrients, water and ions respectively, which is consistent with the clinical signs of PE [1–8]. However, the affected upstream cellular pathway leading to enhanced crypt cell proliferation, altered cell differentiation and homeostasis is still unknown.…”