Salmonella Enteritidis foodborne infection induces altered placental morphometrics in the murine model.

INTRODUCTION: Salmonella foodborne disease during pregnancy causes a significant fetal loss in domestic livestock and preterm birth, chorioamnionitis and miscarriage in humans. These complications could be associated with alterations in placental structure. This study was aimed to determine how a low dose of Salmonella Enteritidis during late gestation affects placental histomorphometric in mice. METHODS: We used a self-limiting enterocolitis murine model. BALB/c pregnant animals received a low dose of Salmonella Enteritidis (3-4 x 102 CFU/mouse) on gestational day (GD) 15. At day 3 post infection bacterial loads, serum cytokines expression and placental histomorphometrics parameters were analyzed. RESULTS: We found that a sub-lethal infection with Salmonella induced a significant drop in fetal weight -to-placental weight-ratio and an increase in the placental coefficient. After bacterial inoculation maternal organs were colonized, inducing placental morphometric alterations, including increased placental thickness, reduced surface area, and diminished major and minor diameters. Also, foci of necrosis accompanied by acute leukocyte infiltration in decidual zone, reduction of vascular spaces and vascular congestion in labyrinth zone, were also evident in placentas from infected females on GD 18. Our data shows that placentas from infected mothers are phenotypically different from control ones. Furthermore, expression of IFN-gamma and IL-6 was up regulated in response to Salmonella in maternal serum. DISCUSSION: Our findings demonstrate that a low dose of Salmonella during late gestation alters the placental morphometry leading to negative consequences on pregnancy outcome such as significant reduction in fetal body weight.

Dam and its role in pathogenicity of Salmonella enterica.

Dam methylation is an essential factor involved in the virulence of an increasing number of bacterial pathogens including Salmonella enterica. Lack of Dam methylation causes severe attenuation in animal models. It has been proposed that dysregulation of Dam activity is potentially a general strategy for the generation of vaccines against bacterial pathogens. In this review, we focus our attention on the role of methylation by Dam protein in regulating bacterial gene expression and virulence in Salmonella enterica.

Sublethal infection with Salmonella Enteritidis by the natural route induces intestinal and joint inflammation in mice.

Reactive arthritis (ReA) is a sterile inflammation triggered by a distal mucosal infection, which suggests a contribution from bacterial products. Investigation on the pathogenesis of ReA is difficult because of the limited studies that can be performed in humans; therefore the availability of animal models is crucial. We hereby describe a murine model for studying the early stages of Salmonella-induced ReA. BALB/c mice infected by the natural route with a sublethal dose of S. Enteritidis showed long lasting gut inflammation, synovitis in the knee joint and a significant increase of CD4+ lymphocytes in the draining popliteal lymph nodes. S. Enteritidis infection induced histological changes in intact knees and exacerbated inflammation in previously damaged joints. Experiments performed with S. Enteritidis DeltainvG mutant suggest that the proinflammatory signalling mediated by Salmonella TTSS-1 in the gut is required for the induction of joint sequelae. Since this model is highly reproducible and easy to perform, it provides great potential for investigating both host and bacterial contributions to the early stages of ReA.

Host response to a dam mutant of Salmonella enterica serovar enteritidis with a temperature-sensitive phenotype.

The temperature-sensitive dam mutant strain of Salmonella enterica serovar Enteritidis SD1 is highly attenuated and induces innate and protective immunity in mice. SD1 activates NF-kappaB and induces gamma interferon secretion. Early interaction of the SD1 mutant with intestinal epithelial cells was associated with ruffling of enterocytes. Invading bacteria were found inside Peyer's patches after inoculation.

Involvement of intestinal inducible nitric oxide synthase (iNOS) in the early stages of murine salmonellosis.

Local induction of inducible nitric oxide synthase (iNOS) and apoptosis was examined in the intestine of mice infected with virulent Salmonella enterica serovar Enteritidis 5694 (S. enteritidis) and its attenuated derivative mutant E/1/3. Both, intestinal iNOS mRNA expression and iNOS activity showed a peak at 4 h only in animals receiving the virulent S. enteritidis. Aminoguanidine treatment abrogated intestinal epithelial damage produced by virulent S. enteritidis and diminished apoptosis at the tips of the villi. Unlike the virulent strain, mutant E/1/3 induced massive iNOS expression in Peyer's patches, these findings may be related to its protective capacity. Our results suggest that intestinal iNOS participates in the early response to intestinal infection and that the final effect depends on the nature of the insult.

VMP1 expression correlates with acinar cell cytoplasmic vacuolization in arginine-induced acute pancreatitis.

BACKGROUND: Recently, we described the cloning of VMP1 (vacuole membrane protein 1). In vitro expression of VMP1 promotes formation of cytoplasmic vacuoles followed by cell death. In order to test if VMP1 expression is related to the cytoplasmic vacuolization of the acinar cells during acute pancreatitis, we studied the in vivo expression of the new gene during arginine-induced acute pancreatitis. METHODS: Male Wistar rats injected with 500 mg/100 g of L-arginine were time-course sacrificed and pancreas tissue removed. RESULTS: Northern blot analysis showed maximal induction of VMP1 after 24 h remaining high after 48 h of arginine administration. Significant increase in the number of TUNEL-stained cells were found at those periods. After 24 and 48 h of arginine administration, light micrographs from thin plastic toluidine blue sections revealed numerous vacuoles in the cytoplasm of acinar cells. In situ hybridization studies showed high expression of VMP1 in acinar cells with cytoplasmic vacuolization. VMP1 mRNA highly and significantly correlated with vacuole formation. CONCLUSION: These results suggest that VMP1 expression may be involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis.