Intracellular signaling mechanisms regulating toll-like receptor-mediated activation of eosinophils

Am J Respir Cell Mol Biol. 2007 Jul;37(1):85-96. doi: 10.1165/rcmb.2006-0457OC. Epub 2007 Mar 1.


Activation of eosinophils by microbe-derived molecules via Toll-like receptors (TLR) potentially provides the link between microbe-induced innate immune responses and the exacerbation of allergic inflammation. We investigated the expression of TLRs and the effect of their ligands on human eosinophils. Expression of TLR1-9 was detected by Western blot and flow cytometry. Adhesion molecules, cytokines, superoxides, and eosinophlilic cationic protein (ECP) were assessed by flow cytometry, enzyme-linked immunosorbent assay, chemiluminescent method, and fluorescence immunoassay, respectively. Human eosinophils differentially expressed TLR1, -2, -4, -5, -6, -7, and -9. Peptidoglycan (PGN) (TLR2 ligand), flagellin (TLR5 ligand), and Imiquimod R837 (TLR7 ligand) could significantly upregulate cell surface expression of intercellular adhesion molecule (ICAM)-1 and CD18, and induce the release of IL-1beta, IL-6, IL-8, growth-related oncogene (GRO)-alpha, and superoxides of eosinophils. Only PGN could induce the degranulation for ECP release. However, ds poly I-C (TLR3 ligand), LPS (TLR4 ligand), ssRNA (TLR8 ligand), and CpG-DNA (TLR9 ligand) were much less effective or inactive. PGN, flagellin, and R837 could activate both nuclear factor (NF)-kappaB and extracellular signal-regulated protein kinase (ERK). PGN could activate phosphatidylinositol 3-kinase (PI3K)-Akt, and R837 both PI3K-Akt and p38 mitogen-activated protein kinase (MAPK). The induction of the release of IL-1beta, IL-6, IL-8, GRO-alpha, superoxides, and ECP by PGN, flagellin, and R837 was found to be differentially regulated by NF-kappaB, ERK, PI3K-Akt, and p38 MAPK. The above results therefore support that microbial infection may lead to the exacerbation of allergic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology
  • CD18 Antigens / biosynthesis
  • Cell Membrane / metabolism
  • Chemokine CXCL1
  • Chemokines, CXC / metabolism
  • Eosinophil Cationic Protein / metabolism
  • Eosinophils / cytology*
  • Eosinophils / metabolism
  • Humans
  • Imiquimod
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • MAP Kinase Signaling System
  • Neutrophils / cytology
  • Signal Transduction*
  • Toll-Like Receptors / metabolism*


  • Aminoquinolines
  • CD18 Antigens
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Toll-Like Receptors
  • Intercellular Adhesion Molecule-1
  • Eosinophil Cationic Protein
  • Imiquimod