P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation.

Despite the growing knowledge with regard to the immunomodulatory properties of host defense peptides, their impact on macrophage differentiation and on its associated microbicidal functions is still poorly understood. Here, we demonstrated that the P17, a new cationic antimicrobial peptide from ant venom, induces an alternative phenotype of human monocyte-derived macrophages (h-MDMs). This phenotype is characterized by a C-type lectin receptors (CLRs) signature composed of mannose receptor (MR) and Dectin-1 expression. Concomitantly, this activation is associated to an inflammatory profile characterized by reactive oxygen species (ROS), interleukin (IL)-1ß, and TNF-α release. P17-activated h-MDMs exhibit an improved capacity to recognize and to engulf Candida albicans through the overexpression both of MR and Dectin-1. This upregulation requires arachidonic acid (AA) mobilization and the activation of peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor through the leukotriene B4 (LTB4) production. AA/LTB4/PPARγ/Dectin-1-MR signaling pathway is crucial for P17-mediated anti-fungal activity of h-MDMs, as indicated by the fact that the activation of this axis by P17 triggered ROS production and inflammasome-dependent IL-1ß release. Moreover, we showed that the increased anti-fungal immune response of h-MDMs by P17 was dependent on intracellular calcium mobilization triggered by the interaction of P17 with pertussis toxin-sensitive G-protein-coupled receptors on h-MDMs. Finally, we also demonstrated that P17-treated mice infected with C. albicans develop less severe gastrointestinal infection related to a higher efficiency of their macrophages to engulf Candida, to produce ROS and IL-1ß and to kill the yeasts. Altogether, these results identify P17 as an original activator of the fungicidal response of macrophages that acts upstream PPARγ/CLRs axis and offer new immunomodulatory therapeutic perspectives in the field of infectious diseases.

Natural orifice transluminal endoscopic surgery (NOTES): assessment of peritoneal bacterial load after intraperitoneal antimicrobial wash and evaluation of hemodynamic changes in a porcine model.

AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is a promising newly developed procedure; however, it is associated with many complications. The main aim of our study is to assess whether peritoneal wash with antibiotics decreases the bacterial load contamination related to the transgastric approach. METHODS: Ten female farm pigs underwent transgastric peritoneoscopy with fallopian tubal ligation. Five pigs were randomized to antibiotic wash of the peritoneal cavity and five to placebo. All animals were given one intravenous dose of antibiotic before the procedure. Hemodynamic variables were continuously monitored throughout the procedure. The next day, peritoneal cultures were taken. The fallopian tubes were inspected to determine the success of ligation and the gastric incision sites were assessed for leakage. RESULTS: No significant difference was noted between the antibiotic peritoneal wash group and the placebo group in terms of peritoneal bacterial load with respective median colony-forming units per ml (CFU/ml) of 0 [0; 1] vs. 0 [0; 4], p = 0.637. No clinically significant hemodynamic changes were noted during the procedure. CONCLUSIONS: The results of our study indicate that NOTES carries minimal risk of peritoneal bacterial contamination, regardless of the use of intraperitoneal antibiotics, and is not associated with hemodynamic compromise.