Induction of interferon-λ contributes to toll-like receptor 3-mediated herpes simplex virus type 1 inhibition in astrocytes
✍ Scribed by Jieliang Li; Li Ye; Xu Wang; Shuxian Hu; Wenzhe Ho
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 625 KB
- Volume
- 90
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Toll‐like receptor 3 (TLR3) recognizes double‐stranded RNA and induces type I interferon (IFN)‐mediated antiviral immunity against a number of viral infections. Type III IFN (IFN‐λ) is a newly identified antiviral cytokine that has biological functions similar to those of type I IFNs. We thus investigated the role of IFN‐λ in TLR3 activation‐mediated inhibition of herpes simplex virus type 1 (HSV‐1) in human primary astrocytes. Human astrocytes express endogenous IFN‐λ1 and IFN‐λ receptor complex, interleukin‐28 receptor α subunit (IL‐28Rα), and IL‐10Rβ. The activation of TLR3 by poly‐I:C treatment significantly induced the expression of IFN‐λ1 and IFN‐λ2/3 in astrocytes. The induction of IFN‐λ contributed to TLR3 activation‐mediated HSV‐1 inhibition in astrocytes. Investigation of the mechanisms showed that treatment of astrocytes with specific antibody against IFN‐λ receptor attenuated the anti‐HSV‐1 activity of poly‐I:C, indicating that endogenous IFN‐λ contributes to the anti‐HSV‐1 effect of TLR3 activation. The anti‐HSV‐1 effect of endogenous IFN‐λ was also confirmed by the finding that recombinant IFN‐λ treatment inhibited HSV‐1 infection of astrocytes. These results provide direct and compelling evidence that endogenous IFN‐λ participates in TLR3‐mediated antiviral activity, which may have important implications in host cell innate immunity against HSV‐1 infection in the CNS. © 2011 Wiley Periodicals, Inc.