S. Typhimurium challenge in juvenile pigs modulates the expression and localization of enteric cholinergic proteins and correlates with mucosal injury and inflammation

• Published in: Autonomic neuroscience 2018-09, Vol.213, p.51-59
• Main Authors: Pohl, Calvin S., Lennon, Elizabeth M., Li, Yihang, DeWilde, Morgan P., Moeser, Adam J.
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; Animals; Body Temperature; Choline O-Acetyltransferase - metabolism; Cholinergic; Female; Gene Expression Regulation; Ileum - metabolism; Ileum - pathology; Inflammation - metabolism; Inflammation - pathology; Inflammation - veterinary; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Lymph Nodes - metabolism; Male; Mucosal inflammation; Porcine intestine; Receptors, Muscarinic - metabolism; Salmonella enterica Typhimurium; Salmonella Infections, Animal - metabolism; Salmonella Infections, Animal - pathology; Salmonella typhimurium; Serogroup; Sus scrofa; Swine; Swine Diseases - metabolism; Swine Diseases - pathology
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2018.05.009

The cholinergic system plays a central role in regulating critical gastrointestinal functions, including motility, secretion, barrier and immune function. In rodent models of acute, non-infectious gastrointestinal injury, the cholinergic system functions to inhibit inflammation; however, during inflammation local expression and regulation of the cholinergic system is not well known, particularly during infectious enteritis. The objective of this study was to determine the intrinsic expression of the enteric cholinergic system in pig ileum following an acute challenge with Salmonella enterica serovar Typhimurium DT104 (S. Typhimurium). At 2 d post-challenge, a three-fold reduction in ileal acetylcholine (ACh) levels was observed in challenged animals, compared with controls. Ileal acetylcholinesterase (AChE) activity was decreased (by four-fold) while choline acetyltransferase (ChAT) expression was increased in both the ileum and mesenteric lymph nodes. Elevated ChAT found to localize preferentially to mucosa overlying lymphoid follicles of the Peyers patch in challenged pigs, with more intense labeling for ChAT in S. Typhimurium challenged pigs compared to controls. Ileal mRNA gene expression of muscarinic receptor 1 and 3 was also increased in challenged pigs, while muscarinic receptor 2 and the nicotinic receptor alpha 7 subunit gene expression were unaffected. A positive correlation was observed between ChAT protein expression in the ileum, rectal temperature, and histopathological severity in challenged animals. These data show that inflammation from S. Typhimurium challenge alters enteric cholinergic expression by down-regulating acetylcholine concentration and acetylcholine degrading enzymes while increasing acetylcholine synthesis proteins and receptors. Given the known anti-inflammatory role of the cholinergic system, the divergent expression of cholinergic genes may represent an attempt to limit tissue damage by preserving cholinergic signaling in the face of low ligand availability. Alterations in the enteric cholinergic system induced by Salmonella Typhimurium challenge in pigs. Salmonella Typhimurium challenge and invasion triggers immune cell recruitment, inflammation and mucosal injury including epithelial cell loss. Subsequent reduction in acetylcholine (ACh) concentrations in the mucosa may induce a compensatory response to preserve and (or) amplify cholinergic signaling by (1) upregulating ACh synthesis via choline acetyltransferase (ChAT)