Multifaceted innate immune responses engaged by astrocytes, microglia and resident dendritic cells against Chikungunya neuroinfection
Autor(es): Das Trina, Hoarau Jean Jacques, Jaffar B-jee Marie Christine, Maquart Marianne, Gasque Philippe
Resumo: Chikungunya virus (CHIKV) has recently affected millions of people in the Indian Ocean, with rare cases of encephalopathy - encephalitis occurring in neonates. In the study described herein, the capacity of mouse brain cells to control infection through innate immune antiviral responses was assessed. In vitro, CHIKV principally infected a subpopulation of mouse GFAP+ primary astrocytes. Oligodendrocytes - neurons could also be infected. An innate immune response was engaged by CHIKV-infected astrocytes with elevated expression of mRNAs for IFN-?-?, inflammatory cytokines (e.g. IL-1?, IL-12, IL-10, IL-24) - proapoptotic factors (e.g. TNF-?, FasL, Lymphotoxin B). Programmed cell death through the intrinsic caspase-9 pathway was observed by immunofluorescence in infected astrocytes - neurons but not in oligodendrocytes. Interestingly, microglia did not replicate CHIKV but responded by elevated mitogen-activated protein kinase (MAPK) activity. Intracerebroventricular injection of CHIKV in neonate mice led to the infection of astrocytes. The astrogliosis response was accompanied by a dendritic CD206+ cell mobilization restricted to the site of infection. The results of this study support the paradigm that a multifaceted innate immune response can be mobilized by both professional immune - glial cells to control CHIKV neuroinfection events in neonates.
Imprenta: The Journal of General Virology, v. 96, n. Pt 2, p. 294-310, 2015
Identificador do objeto digital: 10.1099/vir.0.071175-0
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Cytokines ; Chikungunya virus - Immune response ; Chikungunya virus - Immunopathology ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2015