Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 333, Issue -, Pages -Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2019.576969
Keywords
Monocyte; Astrocyte; Co-culture; Imiquimod; Interferon-alpha; IL-lbeta
Categories
Funding
- National Institutes of Drug Abuse [DA047180]
- National Institutes of Environmental Health Sciences Training Grant [T32 ES07255]
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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-alpha), 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-alpha, promote astrocyte secretion of MCP-1, IL-6 and IP-10. Furthermore, TLR7-induced monocyte-derived IL-1 beta is critical for promoting the astrocyte response. Overall, this study provides a potential mechanism for TLR7-mediated neuroinflammation.
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