TY  - JOUR
AU  - Naujoks, J
AU  - Tabeling, C
AU  - Dill, BD
AU  - Hoffmann, C
AU  - Brown, AS
AU  - Kunze, M
AU  - Kempa, S
AU  - Peter, A
AU  - Mollenkopf, H-J
AU  - Dorhoi, A
AU  - Kershaw, O
AU  - Gruber, AD
AU  - Sander, LE
AU  - Witzenrath, M
AU  - Herold, S
AU  - Nerlich, A
AU  - Hocke, AC
AU  - van Driel, I
AU  - Suttorp, N
AU  - Bedoui, S
AU  - Hilbi, H
AU  - Trost, M
AU  - Opitz, B
Y2  - 2021/02/03
Y1  - 2016/02/01
SN  - 1553-7366
UR  - http://hdl.handle.net/11343/258941
AB  - 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.
LA  - English
PB  - PUBLIC LIBRARY SCIENCE
T1  - IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid
DO  - 10.1371/journal.ppat.1005408
IS  - PLoS Pathogens
VL  - 12
IS  - 2
L1  - /bitstream/handle/11343/258941/PMC4734697.pdf?sequence=1&isAllowed=y
ER  -