Imiquimod and interferon-alpha augment monocyte-mediated astrocyte secretion of MCP-1, IL-6 and IP-10 in a human co-culture system

Abstract

Toll-like receptor 7 (TLR7)-activation has been implicated as a significant mechanism of neuroinflammation triggered by ssRNA viruses. Infiltration of monocytes into the brain and astrocyte activation occurs during in vivo TLR7-mediated neuroinflammation. The objective here was to determine whether the TLR7 agonist, imiquimod, and interferon-alpha (IFN-α), promote monocyte-mediated astrocyte secretion of pro-inflammatory factors. Using a human primary co-culture system, we demonstrate that monocytes, together with imiquimod and IFN-α, promote astrocyte secretion of MCP-1, IL-6 and IP-10. Furthermore, TLR7-induced monocyte-derived IL-1β is critical for promoting the astrocyte response. Overall, this study provides a potential mechanism for TLR7-mediated neuroinflammation.