NLRP3-dependent pyroptosis is required for HIV-1 gp120-induced neuropathology.
Cell Mol Immunol
; 17(3): 283-299, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31320730
ABSTRACT
The human immunodeficiency virus-1 (HIV-1) envelope protein gp120 is the major contributor to the pathogenesis of HIV-associated neurocognitive disorder (HAND). Neuroinflammation plays a pivotal role in gp120-induced neuropathology, but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown. Here, we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy. Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1ß production in microglia. Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury. Importantly, we showed that chronic administration of MCC950, a novel selective NLRP3 inhibitor, to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function. In conclusion, our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína gp120 de Envoltorio del VIH
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VIH-1
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Trastornos Neurocognitivos
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Piroptosis
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Proteína con Dominio Pirina 3 de la Familia NLR
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Cell Mol Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China