RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation.
Cell
; 169(2): 301-313.e11, 2017 Apr 06.
Article
en En
| MEDLINE
| ID: mdl-28366204
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fiebre del Nilo Occidental
/
Virus del Nilo Occidental
/
Proteína Serina-Treonina Quinasas de Interacción con Receptores
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos