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Updated: May 10, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
MGL signaling augments TLR2-mediated responses for enhanced IL-10 and TNF-α secretion
Sandra J van Vliet1, Sylvie Bay, Ilona M Vuist
1VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, the Netherlands. s.vanvliet@vumc.nl
Abstract:
DCs orchestrate immune responses to infectious pathogens and disturbances in tissue integrity. Equipped with C-type lectins, DCs can respond to environmental changes in glycosylation. Many C-type lectins are capable of modulating TLR activation, thereby facilitating tailor-made immune reactions. Here, we investigated the signaling properties of the C-type lectin MGL and show that MGL engagement by agonistic antibodies or carbohydrate ligands couples to TLR signal transduction for increased IL-10 and TNF-α secretion by human monocyte-derived DCs. MGL triggering especially synergized with TLR2-induced pathways, leading to elevated IL-10 mRNA levels and enhanced TNF-α mRNA stability. In addition, MGL signaling promoted phosphorylation of the MAPK ERK and the transcription factor CREB. Whereas specific inhibitors of p90RSK blocked the MGL-induced cytokine secretion, AP-1 was not involved. Strikingly, NF-κB was only crucial for the IL-10 response and dispensable for TNF-α production. Together, our results demonstrate that MGL activation of the ERK-p90RSK-CREB axis converges with TLR2-induced pathways, thereby fine-tuning the DC maturation phenotype.
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