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

Abstract:

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(2+) ions and that inhibition of Ca(2+)-dependent calmodulin activity led to reduced lipid-raft formation. We identify a single-nucleotide polymorphism in the human FLOT1 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem cell transplant recipients. Collectively, flotillin-dependent microdomains on the phagolysosomal membrane play an essential role in protective antifungal immunity.

SEEK ID: https://funginet.hki-jena.de/publications/161

PubMed ID: 32814035

Projects: B4, FungiNet A - Aspergillus projects

Publication type: Not specified

Journal: Cell Rep

Citation: Cell Rep. 2020 Aug 18;32(7):108017. doi: 10.1016/j.celrep.2020.108017.

Date Published: 18th Aug 2020

Registered Mode: Not specified

Authors: F. Schmidt, A. Thywissen, M. Goldmann, C. Cunha, Z. Cseresnyes, H. Schmidt, M. Rafiq, S. Galiani, M. H. Graler, G. Chamilos, J. F. Lacerda, A. Jr Campos, C. Eggeling, M. T. Figge, T. Heinekamp, S. G. Filler, A. Carvalho, A. A. Brakhage

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Created: 16th Feb 2021 at 16:12

Last updated: 17th Jan 2024 at 10:24

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