Filters

2014 - 20202

More filters

2020 - 20212
Reset filters

Settings

Subject: macrophage × WGL Institute: IPHT ×

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections
    (Maryland Heights, MO : Cell Press, 2020) Schmidt, Franziska; Thywißen, Andreas; Goldmann, Marie; Cunha, Cristina; Cseresnyés, Zoltán; Schmidt, Hella; Rafiq, Muhammad; Galiani, Silvia; Gräler, Markus H.; Chamilos, Georgios; Lacerda, João; Campos, António, Jr.; Eggeling, Christian; Figge, Marc Thilo; Heinekamp, Thorsten; Filler, Scott G.; Carvalho, Agostinho; Brakhage, Axel A.
    Schmidt el al. show that lipid rafts in phagolysosomal membranes of macrophages depend on flotillins. Lipid rafts are required for assembly of vATPase and NADPH oxidase. Conidia of the human-pathogenic fungus Aspergillus fumigatus dysregulate assembly of flotillin-dependent lipid rafts in the phagolysosomal membrane and can thereby escape phagolysosomal digestion. © 2020 The Author(s)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 Ca2+ ions and that inhibition of Ca2+-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. © 2020 The Author(s)
  • Thumbnail Image
    Item
    Vinculin binding angle in podosomes revealed by high resolution microscopy
    (San Francisco, CA : Public Library of Science, 2014) Walde, M.; Monypenny, J.; Heintzmann, R.; Jones, G.E.; Cox, S.
    Podosomes are highly dynamic actin-rich adhesive structures formed predominantly by cells of the monocytic lineage, which degrade the extracellular matrix. They consist of a core of F-actin and actin-regulating proteins, surrounded by a ring of adhesion-associated proteins such as vinculin. We have characterised the structure of podosomes in macrophages, particularly the structure of the ring, using three super-resolution fluorescence microscopy techniques: stimulated emission depletion microscopy, structured illumination microscopy and localisation microscopy. Rather than being round, as previously assumed, we found the vinculin ring to be created from relatively straight strands of vinculin, resulting in a distinctly polygonal shape. The strands bind preferentially at angles between 116° and 135°. Furthermore, adjacent vinculin strands are observed nucleating at the corners of the podosomes, suggesting a mechanism for podosome growth.