Ex vivo perfusion of the isolated rat small intestine as a novel model ofSalmonellaenteritis

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.

An ex vivo porcine spleen perfusion as a model of bacterial sepsis

“…Organ perfusion infection models have been developed in the past, both with rodent and human organs. Mouse liver and rat intestine have been tested respectively with Candida albicans and Salmonella enteritidis to investigate host-pathogen interactions (Schwocho and Moon, 1981;Boyle et al, 2016), while human spleen was infected with the parasite Plasmodium falciparum to test organ clearance and processing functionality in pathophysiological conditions (Buffet et al, 2006). The rodent organ perfusions did not overcome the limitations of studying infectious diseases in a poorly relevant model, and the human system is limited by human sample availability.…”

Assessment of Histopathological Changes in the Liver and Spleen of Mice Infected with Salmonella typhi Following Treatment with Ciprofloxacin

“…The actual dosage was confirmed using the plating of serial dilutions of the inoculum, and prepared the LD50 dose of mic. The mice were gavaged with 0.2ml of Salmonella typhi suspension according to the LD50 dose, while the control group was gavaged with the same amount of sterile saline [10,11]. Colonies of bacteria were recovered from the intestines of mice.…”

A novel histidine–tryptophan–ketoglutarate formulation ameliorates intestinal injury in a cold storage and ex vivo warm oxygenated reperfusion model in rats

“…For this purpose, a small bowel warm oxygenated reperfusion system was used to mimic early post-transplant conditions. This reperfusion system has already been certified technically accessible, stable and was widely used [41][42][43][44][45]. Both structure and function relevant parameters proved to be easily accessible.…”