Journal article
IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid
J Naujoks, C Tabeling, BD Dill, C Hoffmann, AS Brown, M Kunze, S Kempa, A Peter, HJ Mollenkopf, A Dorhoi, O Kershaw, AD Gruber, LE Sander, M Witzenrath, S Herold, A Nerlich, AC Hocke, I van Driel, N Suttorp, S Bedoui Show all
Plos Pathogens | Published : 2016
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-..
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Awarded by Medical Research Council
Funding Acknowledgements
This work was supported by the International Max Planck Research School for Infectious Diseases and Immunology (IMPRS-IDI; to JN), and the German Research Foundation (DFG; SPP1580/OP86/10-1 to BO, SFB/TR84 to BO, MW, ACH, ADG, LES, and SPP1580/HI1511/3-1 to HH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.