No abstract

SummaryShigella flexneri is an enteric pathogen that causes massive inflammation and destruction of the human intestinal epithelium. Neutrophils are the first cells of the innate immune system recruited to the site of infection. These cells can attack microbes by phagocytosis, Neutrophil Extracellular Trap (NET) formation and degranulation. Here, we investigated how neutrophil degranulation affects virulence and show that exposure of Shigella to granular proteins enhances infection of epithelial cells. During this process, cationic granular proteins bind to the Shigella surface causing increased adhesion which ultimately leads to hyperinvasion. This effect is mediated by changes in the surface charge, since a lipopolysaccharide (LPS) mutant with a negative surface shows enhanced hyperinvasion compared with wild-type Shigella. We propose that Shigella evolved to use host defence molecules to enhance its virulence and subvert the innate immune system.

The profibrotic mediator Galectin-3 (Gal-3) has been associated with aldosterone-mediated vascular inflammation, fibrosis, and stiffness. We evaluated whether the Gal-3 levels and change in Gal-3 as associated with renal denervation can serve as prediction of therapeutic response to renal denervation. A total of 42 patients with resistant hypertension undergoing renal sympathetic denervation (RDN) were included. Blood pressure was evaluated by 24-h ambulatory measurement before RDN and 1, 3 and 6 months after RDN. Treatment response was defined as a drop in systolic ambulatory blood pressure of >5 mm Hg after 6 months. Blood samples were assessed for Gal-3 levels. For the entire group, a significant drop in mean systolic ambulatory blood pressure of 5.2 ± 18.6 mm Hg was observed (p = 0.032). The responder rate was 50% (n = 21). At baseline, Gal-3 levels were significantly higher in responders (14.5 ± 6.0 vs. 10.95 ± 4.6 ng/ml, p = 0.017). There were no significant changes of Gal-3 levels during the follow-up period. The profibrotic biomarker may help to identify patients suitable for RDN.