TY - JOUR
T1 - Host-derived microvesicles carrying bacterial pore-forming toxins deliver signals to macrophages
T2 - a novel mechanism of shaping immune responses
AU - Köffel, René
AU - Wolfmeier, Heidi
AU - Larpin, Yu
AU - Besançon, Hervé
AU - Schoenauer, Roman
AU - Babiychuk, Viktoria S
AU - Drücker, Patrick
AU - Pabst, Thomas
AU - Mitchell, Timothy J
AU - Babiychuk, Eduard B
AU - Draeger, Annette
PY - 2018/7/27
Y1 - 2018/7/27
N2 - Bacterial 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.
AB - Bacterial 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.
KW - macrophage polarization
KW - microvesicles
KW - liposomes
KW - bacterial pore-forming toxins
KW - host-defense
U2 - 10.3389/fimmu.2018.01688
DO - 10.3389/fimmu.2018.01688
M3 - Article
C2 - 30100903
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1688
ER -