Abstract
West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu‐like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age‐related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous system (CNS) is unknown. Here, we show that aged mice exhibit increased peripheral organ and CNS tissue viral burden, the latter of which is associated with alterations in activation of both myeloid and lymphoid cells compared with similarly infected younger animals. Aged mice exhibit lower MHCII expression by microglia, and higher levels of PD1 and lower levels of IFNγ expression by WNV‐specific CD8+ T cells in the CNS and CD8+CD45+ cells. These data indicate that the aged CNS exhibits limited local reactivation of T cells during viral encephalitis, which may lead to reduced virologic control at this site.
Highlights
West Nile virus (WNV), a mosquito-transmitted RNA virus belonging to the Flaviviridae family, is responsible for recurring outbreaks of meningitis and encephalitis each summer in the United States and parts of Eastern and Southern Europe (Chancey et al, 2015)
Richner et al detected cell-intrinsic defects in naïve CD4+ T cells as well as reduced cytokine and chemokine levels within draining lymph nodes (DLN), both of which contributed to reduced immune cell accumulation, delayed germinal center development, and decreased immune responses in aged mice compared with younger controls (Richner et al, 2015)
Our results show that aged mice are more susceptible to lethal WNV infection, which correlates with impaired immune response and increased viral titers in the central nervous system (CNS)
Summary
West Nile virus (WNV), a mosquito-transmitted RNA virus belonging to the Flaviviridae family, is responsible for recurring outbreaks of meningitis and encephalitis each summer in the United States and parts of Eastern and Southern Europe (Chancey et al, 2015). Richner et al detected cell-intrinsic defects in naïve CD4+ T cells as well as reduced cytokine and chemokine levels within draining lymph nodes (DLN), both of which contributed to reduced immune cell accumulation, delayed germinal center development, and decreased immune responses in aged mice compared with younger controls (Richner et al, 2015) These age-dependent defects occurred within the first few days of infection, resulting in failure to control WNV infection in peripheral tissues and increased neuroinvasion and lethality in aged mice (Richner et al, 2015). These data suggest that aging impacts the antiviral response of microglia and that viral infection may impact aging processes of CNS resident microglia
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