Lipopolysaccharide-Induced Biliary Factors Enhance Invasion ofSalmonella enteritidisin a Rat Model

Abstract

In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 10 6 to 10 7 CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 g/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P < 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-␣) concentrations were measured by bioassay. Biliary concentrations of TNF-␣ rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-␣ cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

Lack of flagella disadvantages Salmonella enterica serovar Enteritidis during the early stages of infection in the rat

“…Thus, there was rapid distribution throughout the gastrointestinal tract, translocation to the mesenteric lymph nodes and spread to the liver and spleen of the rats. Significant numbers of viable salmonella were detected in the mesenteric lymph nodes even within 1 h of oral infection and in the liver and spleen by 24 h. This systemic appearance of pathogen, particularly in liver and spleen, occurred much sooner than reported previously for conventional rats or mice (Islam et al, 2000;Baumler et al, 1996Baumler et al, , 1997Carter & Collins, 1974;Garcia-Del Portillo et al, 1999). This may be linked to the rat strain used (Hooded-Lister), which has been kept as a closed colony for over 50 years, or perhaps to reduced levels of commensal bacteria in the small intestine (Grant, 1996).…”

“…Enteritidis strains LA5 and S1400 colonized and invaded in a manner generally similar to that seen with other S. Enteritidis or S. Typhimurium strains (Naughton et al, 1995(Naughton et al, , 1996a(Naughton et al, , 2000Havelaar et al, 2001;Islam et al, 2000). Thus, there was rapid distribution throughout the gastrointestinal tract, translocation to the mesenteric lymph nodes and spread to the liver and spleen of the rats.…”

“…Salmonella sp. colonize the whole gastrointestinal tract of the rat and cause disruption of the small intestine epithelium, epithelial cell hyperplasia and infiltration by inflammatory cells (Naughton et al, 1995(Naughton et al, , 1996a(Naughton et al, , 2000Havelaar et al, 2001;Islam et al, 2000). Invasion is mainly via the ileum; large numbers of salmonella reach the mesenteric lymph nodes and moderate numbers spread to and persist in the liver and spleen.…”

“…Rats continue to grow, albeit slowly, and death due to infection is rare, unless health or immune status or gut integrity has been compromised by other factors. Salmonellosis in the rat thus has many similarities to the self-limiting gastroenteritis-type infection common in humans and domesticated animals (Naughton et al, 1995(Naughton et al, , 1996a(Naughton et al, , 2000Havelaar et al, 2001;Islam et al, 2000). Defined fimbriae-(SEF14, SEF17, SEF21, pef and lpf) and/or flagella-deleted mutants of S. Enteritidis and their wild-type parent strains were tested in this infection model.…”

Bile Mediates Intestinal Pathology in Endotoxemia in Rats

“…The other is a model of Salmonella infection, in which external drainage of bile reduced the capacity of organisms to invade the liver and mesenteric lymph nodes after oral infection (10). Obvious questions arise as to the nature and source of the factor(s) in bile which is responsible for the tissue damage.…”