Enteric Pathology and <i>Salmonella</i>-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

Santos, Renato L.; Almeida, Arlindo; Xavier, Mariana N.; Wilson, Ronald P.; Dandekar, Satya; Raffatellu, Manuela; Bäumler, Andreas J.

doi:10.1177/0300985810386468

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…1-3). This dependence on the SPI1 T3SS agrees with findings from other in vivo models of Salmonella-induced enteritis, including cattle (38), rhesus macaques (32), and streptomycin-pretreated mice (1). Epithelial tight junction disruption by S. Typhimurium has been shown in vitro and is also dependent on SPI1 T3SS-delivered effectors (3,30).…”

Section: Discussionsupporting

confidence: 88%

“…1 and 2). Submucosal edema and epithelial erosion have similarly been observed in other in vivo models of S. Typhimurium enteritis including in rhesus macaques (19,31,32), cattle (33,38,41), and streptomycin-pretreated mice (1). Similar to S. Typhimurium infection of rhesus macaques and cattle, in our ex vivo model we observe infection and pathological changes in the small intestine within a short time period.…”

Section: Discussionmentioning

confidence: 67%

“…Therefore this model is unsuitable to probe the mechanisms leading to diarrhea. Fluid secretion in response to S. Typhimurium infection has been observed in ileal loops of rabbits (8,11,12,39,40), rhesus macaques (20,31,32), and calves (5). Data from the calf model in particular has provided significant insight into the virulence factors required for fluid accumulation in the lumen.…”

Section: Discussionmentioning

confidence: 99%

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

Boyle

Dombrowsky

Sarau

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Boyle

Dombrowsky

Sarau

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The ileal loop model has been optimized for many different species, including cows, rabbits, pigs, and primates (15,(106)(107)(108). With this model, animals undergo a surgical procedure in which the ileum is tied into multiple equal loops.…”

Section: Gastroenteritis Modelsmentioning

confidence: 99%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.A nimal models are indispensable tools for assessing candidate vaccines, with preclinical animal safety, immunogenicity, and efficacy data being prerequisite for regulatory agencies such as the U.S. Food and Drug Administration (FDA) prior to undertaking early-stage clinical trials. However, not all animal models are created equal. While some models are highly robust and closely mimic clinical infection, others are contrived and far removed from clinical relevance. Choosing the right animal model for the vaccine under investigation is imperative in determining its safety and/or effectiveness.Salmonella spp. are often used as model organisms to study bacterial pathogenesis and host-microbe interactions, due to the ability of certain Salmonella serovars to readily infect animals. As such, there are a myriad of animal models available to vaccine developers. These range from colonization or lethality models to those involving complex surgical techniques (Table 1). The choice of model is often related not only to relevance but also cost, ethics, housing requirements, and the availability of appropriate technical expertise. While most researchers utilize one model or another, integration of data from multiple animal models can provide a more complete understanding of the safety of a candidate vaccine and/or predict how a potential vaccine may perform in humans. In this minireview, we provide background on Salmonella clinical syndromes and pathogenesis and then summarize the various animal models that have been used for Salmonella vaccine research. We include a brief discussion of the technical aspects, advantages, and limitations of each model, followed by a review of the literature surrounding its use in vaccine evaluation. While there has been considerable development for veterinary Salmonella vaccines, here we will focus solely on vaccines and models for human salmonellosis.

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“…However, inoculation of mice with S. typhimurium results in a systemic infection that is not associated with diarrhea (7), but resembles typhoid fever caused by S. typhimurium in human patients (10). Therefore, aside of a few experimental reports with non-human primates (11, 12), bovine experimental infections became very relevant in this context (13) since cattle respond to NTS infection by developing an enteric disease that is clinically similar to human NTS infections (13, 14). Calves can be either orally infected (15) or subjected to surgical ligation of ileal loops that allow for a more precise assessment of early host responses (14).…”

Section: Introductionmentioning

confidence: 99%

Pathobiology of Salmonella, Intestinal Microbiota, and the Host Innate Immune Response

Santos

2014

Front. Immunol.

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Salmonella is a relevant pathogen under a clinical and public health perspective. Therefore, there has been a significant scientific effort to learn about pathogenic determinants of this pathogen. The clinical relevance of the disease, associated with the molecular tools available to study Salmonella as well as suitable animal models for salmonellosis, have provided optimal conditions to drive the scientific community to generate a large expansion of our knowledge about the pathogenesis of Salmonella-induced enterocolitis that took place during the past two decades. This research effort has also generated a wealth of information on the host immune mechanisms that complements gaps in the fundamental research in this area. This review focus on how the interaction between Salmonella, the microbiota and intestinal innate immunity leads to disease manifestation. As a highly successful enteropathogen, Salmonella actively elicits a robust acute intestinal inflammatory response from the host, which could theoretically lead to the pathogen demise. However, Salmonella has evolved redundant molecular machineries that renders this pathogen highly adapted to the inflamed intestinal environment, in which Salmonella is capable of outcompete resident commensal organisms. The adaptation of Salmonella to the inflamed intestinal lumen associated with the massive inflammatory response that leads to diarrhea, generate perfect conditions for transmission of the pathogen. These conditions illustrate the complexity of the co-evolution and ecology of the pathogen, commensals, and the host.

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Enteric Pathology and Salmonella-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

Cited by 11 publications

References 34 publications

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

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

Animal Models for Salmonellosis: Applications in Vaccine Research

Pathobiology of Salmonella, Intestinal Microbiota, and the Host Innate Immune Response

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