title: Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis.
abstract: Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine.
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany;
authors.forename: Erin C
authors.initials: EC
authors.lastname: Boyle
authors.affiliation: Priority Area Asthma and Allergy, Research Center Borstel, Borstel, Germany;
authors.forename: Heike
authors.initials: H
authors.lastname: Dombrowsky
authors.affiliation: Priority Area Asthma and Allergy, Research Center Borstel, Borstel, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sarau
authors.affiliation: Priority Area Infections, Models of Inflammation, Research Center Borstel, Borstel, Germany; Institute for Experimental Medicine, Christian-Albrechts University Kiel, Kiel, Germany;
authors.forename: Janin
authors.initials: J
authors.lastname: Braun
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
authors.affiliation: Priority Area Asthma and Allergy, Research Center Borstel, Borstel, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany; and.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Lautenschläger
authors.affiliation: Priority Area Infections, Models of Inflammation, Research Center Borstel, Borstel, Germany; Institute for Experimental Medicine, Christian-Albrechts University Kiel, Kiel, Germany; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research (DZIF), Hannover, Germany grassl.guntram@mh-hannover.de.
authors.forename: Guntram A
authors.initials: GA
authors.lastname: Grassl
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004751:Enteritis / Q000382:microbiology / Q000473:pathology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000382:microbiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000473:pathology*; D019779:Salmonella enterica
keywords: Salmonella; Yersinia; ex vivo infection; intestinal inflammation