Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. Academic Article uri icon

Overview

abstract

  • Dendritic cells (DCs) are pivotal in determining the class of an adaptive immune response. However, the molecular mechanisms within DCs that determine this decision-making process are unknown. Here, we demonstrate that distinct Toll-like receptor (TLR) ligands instruct human DCs to induce distinct Th cell responses by differentially modulating mitogen-activated protein kinase signaling. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses.

publication date

  • November 15, 2003

Research

keywords

  • Dendritic Cells
  • MAP Kinase Signaling System
  • Membrane Glycoproteins
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins c-fos
  • Receptors, Cell Surface
  • T-Lymphocytes, Helper-Inducer

Identity

Scopus Document Identifier

  • 0242580118

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.171.10.4984

PubMed ID

  • 14607893

Additional Document Info

volume

  • 171

issue

  • 10