Distinct responses to monocytes to Toll-like receptor ligands and inflammatory cytokines

Cinthia Farina, Diethilde Theil, Barbara Semlinger, Reinhard Hohlfeld, Edgar Meinl

Research output: Contribution to journalArticle

Abstract

In this study we compared the activation of monocytes by different bacterial products via Toll-like receptors (TLR), and by different proinflammatory mediators. In response to TLR-2, -4 and -5 engagement, ∼50% of monocytes produced TNF-α, compared to only 5% after induction with IFN-γ or GM-CSF. Furthermore, a small proportion of monocytes produced IL-10 after stimulation via TLR, but not after stimulation with cytokines. Both TLR-ligands and inflammatory cytokines induced the expression of CD25, CD69, CD80 and, surprisingly, also of CD83, commonly regarded as an activation marker for mature dendritic cells (DC). Conversely, TLR-ligands downregulated CD38, CD86 and ICOS-L. Importantly, signaling lymphocytic activation molecule (SLAM; CD150) was identified as a monocyte activation marker that could be induced ex novo via TLR-2, -4 and -5, but not by single stimulation with monocyte activators like IL-1, TNF-α, IFN-β, IFN-γ, GM-CSF or CD40-L. SLAM expression was transient and required mitogen activated protein kinase (MAPK) p38, but not ERK or JNK, and was surprisingly independent of NF-κB. SLAM+ monocytes, which are absent in blood, were detected in spleen and tonsils, where they could be localized to T-cell areas and germinal centers. Together, by comparing the response of monocytes to TLR-ligands and inflammatory cytokines, we have identified a monocyte activation marker, SLAM, which differs in its inducibility from other monocyte activation markers. SLAM+ monocytes and macrophages were identified for the first time in vivo. Their presence might be a sign of innate immune activation.

Original languageEnglish
Pages (from-to)799-809
Number of pages11
JournalInternational Immunology
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 2004

Keywords

  • Cellular activation
  • Inflammation
  • Innate immunity
  • MAP kinase
  • SLAM

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Distinct responses to monocytes to Toll-like receptor ligands and inflammatory cytokines'. Together they form a unique fingerprint.

  • Cite this