TY - JOUR
T1 - Distinct responses to monocytes to Toll-like receptor ligands and inflammatory cytokines
AU - Farina, Cinthia
AU - Theil, Diethilde
AU - Semlinger, Barbara
AU - Hohlfeld, Reinhard
AU - Meinl, Edgar
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
KW - Cellular activation
KW - Inflammation
KW - Innate immunity
KW - MAP kinase
KW - SLAM
UR - http://www.scopus.com/inward/record.url?scp=2942512621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942512621&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxh083
DO - 10.1093/intimm/dxh083
M3 - Article
C2 - 15096475
AN - SCOPUS:2942512621
VL - 16
SP - 799
EP - 809
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 6
ER -