Publikationsdatenbank

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

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

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

Quelle

PLoS pathogens

Bandzählung: 12

Heftzählung: 2

Seiten: 1 – 27

ISSN: 1553-7374

Sprache

Englisch

Verweise

URL (Volltext): http://journals.plos.org/plospathogens/article/asset?id=10.1371%2Fjournal.ppat.1005408.PDF

DOI: 10.1371/journal.ppat.1005408

Pubmed: 26829557

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

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.