Köffel, RenéRenéKöffel0000-0001-9477-4282Wolfmeier, Heidi AnnemarieHeidi AnnemarieWolfmeierLarpin, Yu-NoëlYu-NoëlLarpinBesançon, HervéHervéBesançonSchönauer, RomanRomanSchönauer0000-0001-5295-9940Babiichuk, ViktoriiaViktoriiaBabiichukDrücker, PatrickPatrickDrückerPabst, Thomas NiklausThomas NiklausPabstMitchell, TJTJMitchellBabiichuk, EduardEduardBabiichukDraeger, AnnetteAnnetteDraeger2024-10-072024-10-072018-07-27https://boris-portal.unibe.ch/handle/20.500.12422/60493Bacterial infectious diseases are a leading cause of death. Pore-forming toxins (PFTs) are important virulence factors of Gram-positive pathogens, which disrupt the plasma membrane of host cells and can lead to cell death. Yet, host defense and cell membrane repair mechanisms have been identified: i.e., PFTs can be eliminated from membranes as microvesicles, thus limiting the extent of cell damage. Released into an inflammatory environment, these host-derived PFTs-carrying microvesicles encounter innate immune cells as first-line defenders. This study investigated the impact of microvesicle- or liposome-sequestered PFTs on human macrophage polarization in vitro. We show that microvesicle-sequestered PFTs are phagocytosed by macrophages and induce their polarization into a novel CD14+MHCIIlowCD86low phenotype. Macrophages polarized in this way exhibit an enhanced response to Gram-positive bacterial ligands and a blunted response to Gram-negative ligands. Liposomes, which were recently shown to sequester PFTs and so protect mice from lethal bacterial infections, show the same effect on macrophage polarization in analogy to host-derived microvesicles. This novel type of polarized macrophage exhibits an enhanced response to Gram-positive bacterial ligands. The specific recognition of their cargo might be of advantage in the efficiency of targeted bacterial clearance.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.1210443010090310.3389/fimmu.2018.01688