Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections.

Humans Membrane Microdomains / metabolism Membrane Proteins / pharmacology Mycoses / drug therapy Phagosomes / metabolism
Aspergillus fumigatus NADPH oxidase calcium signaling conidial melanin flotillin fungal pathogenesis macrophage membrane microdomains phagolysosome vATPase

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
18 08 2020
Historique:
received: 26 11 2019
revised: 03 04 2020
accepted: 17 07 2020
entrez: 20 8 2020
pubmed: 20 8 2020
medline: 29 5 2021
Statut: ppublish

Résumé

Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains. Furthermore, we describe a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia of the important human-pathogenic fungus Aspergillus fumigatus resulting in reduced phagolysosomal acidification. We show that phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca

Identifiants

DOI: 10.1016/j.celrep.2020.108017 PMID: 32814035 PMC: PMC10054021
pubmed: 32814035
pii: S2211-1247(20)31002-0
doi: 10.1016/j.celrep.2020.108017
pmc: PMC10054021
mid: NIHMS1878819
pii:
doi:

Substances chimiques

Membrane Proteins 0
flotillins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108017

Subventions

Organisme : Medical Research Council
ID : MC_UU_00008/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/9
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI073829
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Franziska Schmidt (F)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany.

Andreas Thywißen (A)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany.

Marie Goldmann (M)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany.

Cristina Cunha (C)

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Campus de Gualtar, 4710-057 Braga, Portugal.

Zoltán Cseresnyés (Z)

Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), 07745 Jena, Germany.

Hella Schmidt (H)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany.

Muhammad Rafiq (M)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany.

Silvia Galiani (S)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.

Markus H Gräler (MH)

Department of Anesthesiology and Intensive Care Medicine, Center for Sepsis Control and Care (CSCC) and Center for Molecular Biomedicine (CMB), University Hospital Jena, 07740 Jena, Germany.

Georgios Chamilos (G)

Department of Medicine, University of Crete, and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece.

João F Lacerda (JF)

Serviço de Hematologia e Transplantação de Medula, Hospital de Santa Maria, 1649-035 Lisboa, Portugal, and Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal.

António Campos (A)

Serviço de Transplantação de Medula Óssea (STMO), Instituto Português de Oncologia do Porto, 4200-072 Porto, Portugal.

Christian Eggeling (C)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK; Institute of Applied Optics, Friedrich Schiller University Jena, and Department of Biophysical Imaging, Leibniz Institute of Photonic Technology (IPHT), 07745 Jena, Germany.

Marc Thilo Figge (MT)

Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), 07745 Jena, Germany.

Thorsten Heinekamp (T)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany.

Scott G Filler (SG)

Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance CA 90502, USA; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.

Agostinho Carvalho (A)

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Campus de Gualtar, 4710-057 Braga, Portugal.

Axel A Brakhage (AA)

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (HKI), 07745 Jena, Germany; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University Jena, 07745 Jena, Germany. Electronic address: axel.brakhage@leibniz-hki.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Flotillin-Dependent Membrane Microdomains Are...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Microdomaines membranaires › Flotillin-Dependent Membrane Microdomains Are...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Flotillin-Dependent Membrane Microdomains Are...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Mycoses › Flotillin-Dependent Membrane Microdomains Are...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Phagosomes › Flotillin-Dependent Membrane Microdomains Are...