The Formins FMNL1 and mDia1 Regulate Coiling Phagocytosis of Borrelia burgdorferi by Primary Human Macrophages
| Autor: | Mirko Himmel, Xenia Naj, Stefan Linder, Ann-Kathrin Hoffmann |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Phagocytosis
Immunology Formins macromolecular substances Microbiology Immune system Borrelia burgdorferi Group Borrelia Humans Pseudopodia Borrelia burgdorferi Actin nucleation Cellular Microbiology: Pathogen-Host Cell Molecular Interactions biology Macrophages bacterial infections and mycoses biology.organism_classification Cytoskeletal Proteins Infectious Diseases biology.protein Parasitology MDia1 Carrier Proteins |
| Zdroj: | Infection and Immunity. 81:1683-1695 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01411-12 |
| Popis: | Spirochetes of the Borrelia burgdorferi sensu lato complex are the causative agent of Lyme borreliosis, a tick-borne infectious disease primarily affecting the skin, nervous system, and joints. During infection, macrophages and dendritic cells are the first immune cells to encounter invading borreliae. Phagocytosis and intracellular processing of Borrelia by these cells is thus decisive for the eventual outcome of infection. Phagocytic uptake of Borrelia by macrophages proceeds preferentially through coiling phagocytosis, which is characterized by actin-rich unilateral pseudopods that capture and enwrap spirochetes. Actin-dependent growth of these pseudopods necessitates de novo nucleation of actin filaments, which is regulated by actin-nucleating factors such as Arp2/3 complex. Here, we demonstrate that, in addition, also actin-regulatory proteins of the formin family are important for uptake of borreliae by primary human macrophages. Using immunofluorescence, live-cell imaging, and ratiometric analysis, we find specific enrichment of the formins FMNL1 and mDia1 at macrophage pseudopods that are in contact with borreliae. Consistently, small interfering RNA (siRNA)-mediated knockdown of FMNL1 or mDia1 leads to decreased formation of Borrelia -induced pseudopods and to decreased internalization of borreliae by macrophage s . Our results suggest that macrophage coiling phagocytosis is a complex process involving several actin nucleation/regulatory factors. They also point specifically to the formins mDia1 and FMNL1 as novel regulators of spirochete uptake by human immune cells. |
| Databáze: | OpenAIRE |
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