No abstract

Serotype 4b strains of Listeria monocytogenes have been responsible for most large outbreaks of listeriosis. In L. monocytogenes serotype 4b, gtcA and gltA have been implicated in serotype-specific glycosylation of the teichoic acid of the cell wall with galactose and glucose. In this study, we investigated the impact of mutations in gltA (resulting in absence of glucose on teichoic acid) and gtcA (resulting in absence of galactose, and markedly reduced glucose on teichoic acid) on virulence following intragastric infection of anesthetized A/J mice. The gltA mutant was not impaired in virulence in this model. In contrast, testing of gtcA mutants constructed in two different strains showed that the mutants were recovered in lower numbers than their respective parent strains from the spleen, liver, ceca, and gall bladders of intragastrically inoculated mice. Genetic complementation of the gtcA mutation partially restored gastrointestinal virulence. When mice were inoculated intravenously, the gtcA mutants were also recovered in lower numbers from the liver (for both mutant strains) and the spleen (for one mutant strain) than their respective parental strains. The mutants were also evaluated for invasion and intracellular multiplication in the Caco-2 human intestinal epithelial cell line. Inactivation of gltA did not affect invasion or intracellular growth of the bacteria. In contrast, gtcA mutants showed decreased invasion, but normal multiplication in Caco-2 cells. Overall, these data demonstrate a role for gtcA in the pathogenesis of gastrointestinal listeriosis in mice, and suggest that diminished ability of gtcA mutants to invade intestinal epithelial cells may be partly responsible for decreased gastrointestinal virulence.

The aim of the present study was to investigate the expression levels and clinical significance of Toll-like receptor (TLR) 3 and 4 in peripheral blood mononuclear cells (PBMCs) collected from children with Henoch-Schönlein purpura (HSP) nephritis. The randomized controlled trial was conducted between August 2011 and March 2013, and 105 children with a clinical diagnosis of HSP were enrolled in the study. According to the 24-h urinary protein measurements and the presence of renal damage, the 105 cases were divided into groups A, B and C as follows: Group A, children with HSP but without renal damage; group B, children with HSP nephritis but without proteinuria; group C, children with HSP nephritis and proteinuria. A total of 30 healthy children were enrolled in the normal control group (group N). The primary endpoints were the detection of TLR3 and 4 mRNA and protein expression levels in PBMCs by flow cytometry and quantitative polymerase chain reaction. The mRNA and protein expression levels of TLR4 in the PBMCs were significantly higher in groups A, B and C when compared with group N. In addition, the mRNA and protein expression levels of TLR4 in group C were much higher when compared with groups A and B. A positive correlation was identified between TLR4 protein expression and 24-h urinary protein levels in group C. The expression levels of TLR3 did not significantly differ among the groups. Protein and mRNA expression levels of TLR4 in PBMCs significantly increased and exhibited a positive correlation with urinary protein excretion. These results indicate that aberrant activation of TLR4 may be relevant to the development of HSP nephritis.

ITP patients presented with a high CD4/CD8 ratio and low levels of Tregs and NK cells, suggesting that immune deregulation was involved in the pathogenesis of ITP. The pre-treated immune status of ITP patients may not be related to the curative effect. Tregs significantly increased in the effective group post-treatment, highlighting that the mechanism of restoring Tregs may be involved in the treatment of ITP. However, whether or not the targeted regulation of Tregs is an effective treatment for ITP still requires further studies.