Host-derived microvesicles carrying bacterial pore-forming toxins deliver signals to macrophages: a novel mechanism of shaping immune responses

Research output: Contribution to journalArticle

Authors

  • René Köffel
  • Heidi Wolfmeier
  • Yu Larpin
  • Hervé Besançon
  • Roman Schoenauer
  • Viktoria S Babiychuk
  • Patrick Drücker
  • Thomas Pabst
  • Eduard B Babiychuk
  • Annette Draeger

Colleges, School and Institutes

External organisations

  • Institute of Anatomy; University of Bern; Baltzerstrasse 2 3012 Bern Switzerland
  • Department of Medical Oncology, University Hospital Bern, Bern, Switzerland.
  • College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

Abstract

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.

Details

Original languageEnglish
Article number1688
Number of pages13
JournalFrontiers in immunology
Volume9
Publication statusPublished - 27 Jul 2018

Keywords

  • macrophage polarization, microvesicles, liposomes, bacterial pore-forming toxins, host-defense