Lipopolysaccharide-induced biliary factors enhance invasion of Salmonella enteritidis in a rat model

In this study, the role of the hepatobiliary system in the early pathogenes is of Salmonella enteritidis infection was investigated in a rat model. Int ravenous (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 infect ion 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 s imilarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 mu g/kg of body weight), significant invasion of the livers and m esenteric lymph nodes (MLN) occurred within 24 h, with invasion of the live r 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 mediator s into the bile, biliary tumor necrosis factor alpha (TNF-alpha) concentrat ions were measured by bioassay. Biliary concentrations of TNF-alpha rose sh ortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml a t around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) aft er 2.5 h. Although TNF-alpha cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enter itidis is enhanced by the presence of LPS in the blood and that this enhanc ed invasion is at least in part a consequence of the delivery of inflammato ry mediators to the gastrointestinal tract by the hepatobiliary system.