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.

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

Date Published: 18th Aug 2020

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, Marc Thilo Figge, Thorsten Heinekamp, S. G. Filler, A. Carvalho, Axel Brakhage

Help
help Creator
Activity

Views: 298

Created: 16th Feb 2021 at 16:12

help Attributions

None

Related items

Powered by
(v.1.9.1)
Copyright © 2008 - 2019 The University of Manchester and HITS gGmbH