Journal article
Authors list: 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; Gruber, Achim D.; 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
Publication year: 2016
Journal: PLoS Pathogens
Volume number: 12
Issue number: 2
ISSN: 1553-7366
eISSN: 1553-7374
Open access status: Gold
DOI Link: https://doi.org/10.1371/journal.ppat.1005408
Publisher: Public Library of Science
Abstract:
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.
Citation Styles
Harvard Citation style: Naujoks, J., Tabeling, C., Dill, B., Hoffmann, C., Brown, A., Kunze, M., et al. (2016) IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid, PLoS Pathogens, 12(2), Article e1005408. https://doi.org/10.1371/journal.ppat.1005408
APA Citation style: Naujoks, J., Tabeling, C., Dill, B., Hoffmann, C., Brown, A., Kunze, M., Kempa, S., Peter, A., Mollenkopf, H., Dorhoi, A., Kershaw, O., Gruber, A., Sander, L., Witzenrath, M., Herold, S., Nerlich, A., Hocke, A., van Driel, I., Suttorp, N., ...Opitz, B. (2016). IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid. PLoS Pathogens. 12(2), Article e1005408. https://doi.org/10.1371/journal.ppat.1005408
Keywords
ALVEOLAR MACROPHAGES; BACTERICIDAL ACTIVITY; CELL-AUTONOMOUS IMMUNITY; C VIRUS-REPLICATION; INTRACELLULAR PATHOGENS; MITOCHONDRIAL ROS; PNEUMOPHILA INFECTION; TOXOPLASMA-GONDII
