Journal
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
Volume 3, Issue 1, Pages 5-11Publisher
SPRINGER
DOI: 10.1007/s11481-007-9097-8
Keywords
microglia; toll-like receptors; vaccinia virus; NF-kappa B; HSV
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Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH066703] Funding Source: NIH RePORTER
- NIMH NIH HHS [MH066703, R01 MH066703-07A1, R01 MH066703] Funding Source: Medline
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Microglial cells respond to the herpes simplex virus (HSV)-1 by producing proinflammatory cytokines and chemokines. After this inflammatory burst, these cells undergo apoptotic cell death. We have recently demonstrated that both virus-induced immune mediator production and apoptosis were induced through Toll-like receptor 2 (TLR2) signaling. Based upon these findings, we hypothesized that the inhibition of TLR2 signaling may serve as a means to alleviate excessive neuroinflammation. In the present study, we cloned four vaccinia virus (VV) proteins, which have been reported to disrupt either TLR signaling or NF-kappa B activation, and overexpressed them in HEK293T cells stably expressing murine TLR2 and in primary murine microglia. Using an NF-kappa B-driven luciferase reporter gene assay, we show that upon stimulation with HSV and Listeria monocytogenes, all four vaccinia proteins inhibited TLR2 signaling with different levels of inhibition in the TLR2-expressing cell line and primary microglia. We found similar results when microglial cells were stimulated with the TLR4 ligand LPS and the TLR9 ligand CpG ODN. Taken together, these data provide evidence that these VV proteins can function as inhibitors of TLR signaling in primary microglial cells.
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