Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection

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Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection

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Title: Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection
Author: Lupfer, Christopher; Thomas, Paul G.; Anand, Paras K.; Vogel, Peter; Milasta, Sandra; Martinez, Jennifer; Huang, Gonghua; Green, Maggie; Kundu, Mondira; Chi, Hongbo; Xavier, Ramnik J.; Green, Douglas R.; Lamkanfi, Mohamed; Dinarello, Charles A.; Doherty, Peter C.; Kanneganti, Thirumala-Devi

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
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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.
Published Version: doi:10.1038/ni.2563
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631456/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879094
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