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

(2013) NATURE IMMUNOLOGY. 14(5). p.480-488
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Abstract
NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-kappa B 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 infection with influenza A virus. Ripk2(-/-) cells exhibited defective autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1(-/-) cells exhibited enhanced mitochondrial production of superoxide and activation of caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1-dependent mitophagy.
Keywords
IL-1-BETA PRODUCTION, IMMUNE-RESPONSE, LISTERIA-MONOCYTOGENES, AUTOPHAGY, DOUBLE-STRANDED-RNA, IFN-GAMMA PRODUCTION, 1918 INFLUENZA-VIRUS, CD8(+) T-CELLS, DENDRITIC CELLS, INNATE

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Chicago
Lupfer, Christopher, Paul G Thomas, Paras K Anand, Peter Vogel, Sandra Milasta, Jennifer Martinez, Gonghua Huang, et al. 2013. “Receptor Interacting Protein Kinase 2-mediated Mitophagy Regulates Inflammasome Activation During Virus Infection.” Nature Immunology 14 (5): 480–488.
APA
Lupfer, C., Thomas, P. G., Anand, P. K., Vogel, P., Milasta, S., Martinez, J., Huang, G., et al. (2013). Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. NATURE IMMUNOLOGY, 14(5), 480–488.
Vancouver
1.
Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J, et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. NATURE IMMUNOLOGY. 2013;14(5):480–8.
MLA
Lupfer, Christopher, Paul G Thomas, Paras K Anand, et al. “Receptor Interacting Protein Kinase 2-mediated Mitophagy Regulates Inflammasome Activation During Virus Infection.” NATURE IMMUNOLOGY 14.5 (2013): 480–488. Print.
@article{3215223,
  abstract     = {NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-kappa B 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 infection with influenza A virus. Ripk2(-/-) cells exhibited defective autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1(-/-) cells exhibited enhanced mitochondrial production of superoxide and activation of caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1-dependent mitophagy.},
  author       = {Lupfer, Christopher and Thomas, Paul G and Anand, Paras K and Vogel, Peter and Milasta, Sandra and Martinez, Jennifer and Huang, Gonghua and Green, Maggie and Kundu, Mondira and Chi, Hongbo and Xavier, Ramnik J and Green, Douglas R and Lamkanfi, Mohamed and Dinarello, Charles A and Doherty, Peter C and Kanneganti, Thirumala-Devi},
  issn         = {1529-2908},
  journal      = {NATURE IMMUNOLOGY},
  keywords     = {IL-1-BETA PRODUCTION,IMMUNE-RESPONSE,LISTERIA-MONOCYTOGENES,AUTOPHAGY,DOUBLE-STRANDED-RNA,IFN-GAMMA PRODUCTION,1918 INFLUENZA-VIRUS,CD8(+) T-CELLS,DENDRITIC CELLS,INNATE},
  language     = {eng},
  number       = {5},
  pages        = {480--488},
  title        = {Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection},
  url          = {http://dx.doi.org/10.1038/ni.2563},
  volume       = {14},
  year         = {2013},
}

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