Host-Derived Microvesicles Carrying Bacterial Pore-Forming Toxins Deliver Signals to Macrophages: A Novel Mechanism of Shaping Immune Responses.

Köffel, René; Wolfmeier, Heidi Annemarie; Larpin, Yu Noël; Besançon, Hervé; Schönauer, Roman; Babiychuk, Victoria; Drücker, Patrick; Pabst, Thomas; Mitchell, TJ; Babiychuk, Eduard; Draeger, Annette (2018). Host-Derived Microvesicles Carrying Bacterial Pore-Forming Toxins Deliver Signals to Macrophages: A Novel Mechanism of Shaping Immune Responses. Frontiers in immunology, 9(1688), p. 1688. Frontiers Research Foundation 10.3389/fimmu.2018.01688

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Köffel, René; Wolfmeier, Heidi Annemarie; Larpin, Yu Noël; Besançon, Hervé; Schönauer, Roman; Babiychuk, Victoria; Drücker, Patrick; Pabst Müller, Thomas Niklaus; Babiychuk, Eduard and Draeger, Annette

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

René Köffel

Date Deposited:

09 Nov 2018 08:37

Last Modified:

19 Feb 2019 10:46

Publisher DOI:

10.3389/fimmu.2018.01688

PubMed ID:

30100903

BORIS DOI:

10.7892/boris.121044

URI:

https://boris.unibe.ch/id/eprint/121044

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