CD40-CD40L interactions induce chemokine expression by human microglia: Implications for human immunodeficiency virus encephalitis and multiple sclerosis

Teresa G. D'Aversa, Karen M. Weidenheim, Joan W. Berman

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

CD40 is a protein on microglia that is up-regulated with interferon (IFN)-γ and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-γ and CD40L increased expression of several chemokines. IFN-γ- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-γ- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalAmerican Journal of Pathology
Volume160
Issue number2
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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