Single versus double experimental bile duct ligation model for inducing bacterial translocation

Background: Double common bile duct ligation plus section in rats is used as a model for bacterial translocation, a phenomenon that has been correlated with the degree of liver damage. This study analyzes whether a simpler variant of the technique is also a valid model to study bacterial translocation. Methods: Fifty-six male Sprague Dawley rats underwent one of three surgical interventions: a) proximal double ligation and section of the common bile duct; b) proximal simple ligation of the bile duct; and c) sham operation. Bacterial translocation was measured by cultures of mesenteric lymph nodes, blood, spleen and liver. Stool culture and histological analysis of liver damage were also performed. Results: The incidence of bacterial translocation in SBL and DBDL groups was 23,5% and 25% respectively. Mortality was similar between ligation groups (11.2% versus 10%). Liver cirrhosis developed in the group of double ligation and section (100% of the animals at 4 weeks), while portal hypertension appeared starting at week 3. None of the animals submitted to simple ligation developed liver cirrhosis. Conclusions: Simple bile duct ligation is associated with a similar incidence of bacterial translocation as double ligation, but without cirrhosis or portal hypertension

Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation

Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration. However, the contribution of CAR to lung inflammation remains unclear. Here we investigate the mechanistic contribution of CAR in mediating responses to the common aeroallergen, House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells and decreased pro-inflammatory cytokine release. In vitro analysis in human lung epithelial cells confirms that loss of CAR leads to reduced HDM-dependent inflammatory cytokine release and neutrophil migration. Epithelial CAR depletion also promoted smooth muscle cell proliferation mediated by GSK3β and TGF-β, basal matrix production and airway hyperresponsiveness. Our data demonstrate that CAR coordinates lung inflammation through a dual function in leucocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in inflammatory lung diseases

Modulation of immune responses by targeting CD169/Siglec-1 with the glycan ligand

A fundamental role in the plant-bacterium interaction for Gram-negative phytopathogenic bacteria is played by membrane constituents, such as proteins, lipopoly- or lipooligosaccharides (LPS, LOS) and Capsule Polysaccharides (CPS). In the frame of the understanding the molecular basis of plant bacterium interaction, the Gram-negative bacterium Agrobacterium vitis was selected in this study. It is a phytopathogenic member of the Rhizobiaceae family and it induces the crown gall disease selectively on grapevines (Vitis vinifera). A. vitis wild type strain F2/5, and its mutant in the quorum sensing gene ΔaviR, were studied. The wild type produces biosurfactants; it is considered a model to study surface motility, and it causes necrosis on grapevine roots and HR (Hypersensitive Response) on tobacco. Conversely, the mutant does not show any surface motility and does not produce any surfactant material; additionally, it induces neither necrosis on grape, nor HR on tobacco. Therefore, the two strains were analyzed to shed some light on the QS regulation of LOS structure and the consequent variation, if any, on HR response. LOS from both strains were isolated and characterized: the two LOS structures maintained several common features and differed for few others. With regards to the common patterns, firstly: the Lipid A region was not phosphorylated at C4 of the non reducing glucosamine but glycosylated by an uronic acid (GalA) unit, secondly: a third Kdo and the rare Dha (3-deoxy-lyxo-2-heptulosaric acid) moiety was present. Importantly, the third Kdo and the Dha residues were substituted by rhamnose in a not stoichiometric fashion, giving four different oligosaccharide species. The proportions among these four species, is the key difference between the LOSs from both the two bacteria. LOS from both strains and Lipid A from wild type A. vitis are now examined for their HR potential in tobacco leaves and grapevine roots