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The Journal of general virology

Multifaceted innate immune responses engaged by astrocytes, microglia and resident dendritic cells against Chikungunya neuroinfection.


PMID 25351727

Abstract

Chikungunya virus (CHIKV) has recently affected millions of people in the Indian Ocean, with rare cases of encephalopathy and 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 and neurons could also be infected. An innate immune response was engaged by CHIKV-infected astrocytes with elevated expression of mRNAs for IFN-α-β, inflammatory cytokines (e.g. IL-1β, IL-12, IL-10, IL-24) and proapoptotic factors (e.g. TNF-α, FasL, Lymphotoxin B). Programmed cell death through the intrinsic caspase-9 pathway was observed by immunofluorescence in infected astrocytes and 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 and glial cells to control CHIKV neuroinfection events in neonates.