Identification of a novel negative role of flagellin in regulating IL-10 production

Ildefonso Vicente-Suarez, Yoshinori Takahashi, Fengdong Cheng, Pedro Horna, Hong W. Wang, Hong Gang Wang, Eduardo M. Sotomayor

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Toll-like receptors (TLR) expressed by cells of the immune system play a central role in the generation of immune responses against pathogens. Following TLR ligation, both pro-inflammatory and anti-inflammatory mediators are produced in order to elicit an immune response that controls the microbial infection while limiting tissue damage. Among these mediators, the pro-inflammatory cytokine IL-12 and the anti-inflammatory cytokine IL-10 are known to play major roles. Here, we show that in vitro or in vivo stimulation with flagellin, the TLR5 ligand, does not result in IL-10 production. Furthermore, flagellin inhibits IL-10 production by other specific TLR ligands at the protein and mRNA levels while increasing IL-12p70 production. Several studies have linked the activation of extracellular signal-regulated kinases with IL-10 induction by TLR. We have observed that LPS-induced extracellular signal-regulated kinase activation was significantly decreased in flagellin-treated macrophages, suggesting that this pathway might play a role in the inhibition of IL-10 production observed in flagellin-treated macrophages. Flagellin-mediated IL-10 inhibition was not observed in cells that do not express TLR5, supporting that this effect is indeed TLR5-dependent. This study provides a new insight into the role of flagellin recognition by TLR5 in shaping the immune response elicited by flagellated microorganisms.

Original languageEnglish (US)
Pages (from-to)3164-3175
Number of pages12
JournalEuropean Journal of Immunology
Volume37
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • Flagellin
  • Macrophages
  • TLR5
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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