Fachbereich Veterinärmedizin



    IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid (2016)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Naujoks, Jan
    Tabeling, Christoph
    Dill, Brian D
    Hoffmann, Christine
    Brown, Andrew S
    Kunze, Mareike
    Kempa, Stefan
    Peter, Andrea
    Mollenkopf, Hans-Joachim
    Dorhoi, Anca
    Kershaw, Olivia (WE 12)
    Gruber, Achim D (WE 12)
    Sander, Leif E
    Witzenrath, Martin
    Herold, Susanne
    Nerlich, Andreas
    Hocke, Andreas C
    van Driel, Ian
    Suttorp, Norbert
    Bedoui, Sammy
    Hilbi, Hubert
    Trost, Matthias
    Opitz, Bastian
    PLoS Pathogens; 12(2) — S. 1–27
    ISSN: 1553-7366
    URL (Volltext): http://journals.plos.org/plospathogens/article/asset?id=10.1371%2Fjournal.ppat.1005408.PDF
    DOI: 10.1371/journal.ppat.1005408
    Pubmed: 26829557
    Institut für Tierpathologie

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    Abstract / Zusammenfassung

    Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system. Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection, and activators of an alveolar macrophage-intrinsic immune response that restricts bacterial growth during pneumonia. Quantitative mass spectrometry revealed that both IFNs substantially modify Legionella-containing vacuoles, and comparative analyses reveal distinct subsets of transcriptionally and spatially IFN-regulated proteins. Immune-responsive gene (IRG)1 is induced by IFNs in mitochondria that closely associate with Legionella-containing vacuoles, and mediates production of itaconic acid. This metabolite is bactericidal against intravacuolar L. pneumophila as well as extracellular multidrug-resistant Gram-positive and -negative bacteria. Our study explores the overall role IFNs play in inducing substantial remodeling of bacterial vacuoles and in stimulating production of IRG1-derived itaconic acid which targets intravacuolar pathogens. IRG1 or its product itaconic acid might be therapeutically targetable to fight intracellular and drug-resistant bacteria.