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

Abstract

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.

Musca domestica Cecropin (Mdc) Alleviates Salmonella typhimurium-Induced Colonic Mucosal Barrier Impairment: Associating With Inflammatory and Oxidative Stress Response, Tight Junction as Well as Intestinal Flora

“…It is an invasive bacterium that mainly invades small intestine and colon ( Winter et al, 2010 ). Intestinal mucosal barrier injury frequently occurs following S. typhimurium challenge ( Pohl et al, 2018 ). Although there are many Salmonella infection models that can be used to study different types of intestinal injury ( Santos et al, 2001 ), the S. typhimurium infection model used in this experiment is usually used to establish colonic mucosal lesions ( Manja et al, 2003 ).…”

Potential of a fucoidan-rich Ascophyllum nodosum extract to reduce Salmonella shedding and improve gastrointestinal health in weaned pigs naturally infected with Salmonella

“… bp , Base pairs; Tm , Melting temperature; IL1A , Interleukin 1 alpha; IL6 , Interleukin 6; IL7 , Interleukin 7; CXCL8 , C-X-C motif chemokine ligand 8; IL10 , Interleukin 10; IL17A , Interleukin 17 alpha; IL22 , Interleukin 22; IFNG , Interferon gamma; TNF , Tumour necrosis factor; TGFB1 , Transforming growth factor beta 1; FOXP3 , Forkhead box P3; CCL20 , C-C motif chemokine ligand 20; TLR4 , Toll-like receptor 4; TP53 , Tumour protein p53; STAT3 , Signal transducer and activator of transcription 3; MUC2 , Mucin 2; TJP1 / ZO-1 , Tight junction protein 1/Zona occludens 1; CHRM1 , Cholinergic receptor muscarinic 1; NOX1 , Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1; DUOX2 , Dual oxidase 2; PPIA , Peptidylprolyl isomerase A; B2M , Beta-2-microglobulin; GAPDH , Glyceraldehyde-3-phosphate dehydrogenase a Genes encoding proteins with an established role in facilitating or inhibiting Salmonella infection. These proteins are associated with chemotaxis ( CCL20 ), production of reactive oxygen species ( NOX1 , DUOX2 ) anti-inflammatory activity ( STAT3 , CHRM1 ) and cell survival and death ( TP53 ) [ 54 – 59 ] …”

“…a Genes encoding proteins with an established role in facilitating or inhibiting Salmonella infection. These proteins are associated with chemotaxis ( CCL20 ), production of reactive oxygen species ( NOX1 , DUOX2 ) anti-inflammatory activity ( STAT3 , CHRM1 ) and cell survival and death ( TP53 ) [ 54 – 59 ]…”