Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection
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Author
Lupfer, Christopher
Thomas, Paul G.
Anand, Paras K.
Vogel, Peter
Milasta, Sandra
Martinez, Jennifer
Huang, Gonghua
Green, Maggie
Kundu, Mondira
Chi, Hongbo
Green, Douglas R.
Lamkanfi, Mohamed
Dinarello, Charles A.
Doherty, Peter C.
Kanneganti, Thirumala-Devi
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ni.2563Metadata
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Lupfer, C., P. G. Thomas, P. K. Anand, P. Vogel, S. Milasta, J. Martinez, G. Huang, et al. 2013. “Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection.” Nature immunology 14 (5): 480-488. doi:10.1038/ni.2563. http://dx.doi.org/10.1038/ni.2563.Abstract
NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-κB and MAP kinase signaling during bacterial infections, but the role of this immune axis during viral infections has not been addressed. We demonstrate that Nod2−/− and Ripk2−/− mice are hypersusceptible to influenza A virus infection. Ripk2−/− cells displayed defective mitophagy leading to enhanced mitochondrial superoxide production and accumulation of damaged mitochondria resulting in increased NLRP3 inflammasome activation and IL-18 production. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1−/− cells displayed enhanced mitochondrial superoxide production and caspase-1 activation. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating NLRP3 inflammasome activation and IL-18 production via ULK1-dependent mitophagy.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631456/pdf/Terms of Use
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