Daniels, B. P., Snyder, A. G., Olsen, T. M., Orozco, S., Oguin III, T. H., Tait, S. W.G. , Martinez, J., Gale, M., Loo, Y.-M. and Oberst, A. (2017) RIPK3 restricts viral pathogenesis via cell death-independent neuroinflammation. Cell, 169(2), 301-313.e11. (doi: 10.1016/j.cell.2017.03.011) (PMID:28366204) (PMCID:PMC5405738)
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Abstract
Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3(-/-) mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS.
| Item Type: | Articles |
|---|---|
| Keywords: | RIPK1, RIPK3, West Nile virus, chemokines, necroptosis, neuroimmunology, neuroinflammation. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tait, Professor Stephen |
| Authors: | Daniels, B. P., Snyder, A. G., Olsen, T. M., Orozco, S., Oguin III, T. H., Tait, S. W.G., Martinez, J., Gale, M., Loo, Y.-M., and Oberst, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cell |
| Publisher: | Elsevier |
| ISSN: | 0092-8674 |
| ISSN (Online): | 1097-4172 |
| Published Online: | 30 March 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Cell 169(2):301-313.e11 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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