International Immunology Advance Access originally published online on April 19, 2004
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International Immunology, Vol. 16, No. 6, pp. 799-809,
June 2004
© 2004 Japanese Society for Immunology
Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines
1 Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany, 2 Department of Neurologyand 3 Institute for Clinical Neuroimmunology, Ludwig-Maximilians University, D-81377 Munich, Germany
Correspondence to: E. Meinl; E-mail: meinl{at}neuro.mpg.de
Transmitting editor: G. Hammerling
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-
, compared to only 5% after induction with IFN-
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-, IFN-ß, IFN-, 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-
B. 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.
Keywords: cellular activation, inflammation, innate immunity, MAP kinase, SLAM
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