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

Franziska Schmidt1, Andreas Thywißen1, Marie Goldmann1

  • 1Department 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.

Cell Reports
|August 20, 2020
PubMed

Insights

Flotillins are crucial for macrophage defense against Aspergillus fumigatus by organizing membrane microdomains essential for phagolysosome function. Genetic defects increase susceptibility to invasive aspergillosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Mycology

Background:

  • Lipid rafts are membrane microdomains with roles in cell signaling and immunity.
  • Their function in the immune response to fungal infections is not fully understood.

Purpose of the Study:

  • To investigate the role of lipid-raft microdomains and flotillins in macrophage defense against Aspergillus fumigatus.
  • To elucidate the mechanism by which Aspergillus fumigatus disrupts these microdomains.

Main Methods:

  • Genetic deletion of flotillins in macrophages.
  • Analysis of phagolysosomal acidification and defense complex assembly (vATPase, NADPH oxidase).
  • Investigating the role of calcium ions and calmodulin in lipid raft formation.

Main Results:

  • Flotillins are essential for assembling defense complexes on phagolysosomal membranes.
  • Melanized Aspergillus fumigatus conidia disrupt these microdomains, impairing phagolysosomal acidification.
  • Reduced Ca2+ and calmodulin activity inhibit lipid raft formation.
  • A human FLOT1 polymorphism increases susceptibility to invasive aspergillosis.

Conclusions:

  • Flotillin-dependent lipid rafts on phagolysosomal membranes are critical for antifungal immunity.
  • Aspergillus fumigatus employs a mechanism to evade immune defenses by disrupting these rafts.
  • Genetic variations in FLOT1 impact human susceptibility to invasive fungal infections.
Keywords:
Aspergillus fumigatusNADPH oxidasecalcium signalingconidial melaninflotillinfungal pathogenesismacrophagemembrane microdomainsphagolysosomevATPase

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