Document Type

Article

Publication Date

2009

DOI

10.1016/j.virol.2009.01.032

Publication Title

Virology

Volume

387

Issue

1

Pages

117-126

Abstract

Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45highCD11b+)and CD8+ T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8+ T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

Rights

Elsevier Open Archive. © 2009 Elsevier Inc. All rights reserved.

Article can be accessed at:

https://doi.org/10.1016/j.virol.2009.01.032

Original Publication Citation

Steel, C. D., Hahto, S. M., & Ciavarra, R. P. (2009). Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system. Virology, 387(1), 117-126. doi:10.1016/j.virol.2009.01.032

ORCID

0000-0003-3551-8400 (Steel)

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