Toll-like receptor responses in IRAK-4-deficient neutrophils

J Innate Immun. 2010;2(3):280-7. doi: 10.1159/000268288. Epub 2009 Dec 16.

Abstract

Human neutrophils were found to express all known Toll-like receptors (TLRs) except TLR3 and TLR7. IRAK-4-deficient neutrophils were tested for their responsiveness to various TLR ligands. Essentially all TLR responses in neutrophils, including the induction of reactive oxygen species generation, adhesion, chemotaxis and IL-8 secretion, were found to be dependent on IRAK-4. Surprisingly, the reactivity towards certain established TLR ligands, imiquimod and ODN-CpG, was unaffected by IRAK-4 deficiency, demonstrating their activity is independent of TLR. TLR-4-dependent signaling in neutrophils was totally dependent on IRAK-4 without any major TRIF-mediated contribution. We did not observe any defects in killing capacity of IRAK-4-deficient neutrophils for Staphylococcus aureus, Escherichia coli and Candida albicans, suggesting that microbial killing is primarily TLR independent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Aminoquinolines / pharmacology
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology*
  • Bacterial Infections / metabolism
  • Candida albicans / physiology*
  • Candidiasis / immunology
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Chemotaxis / genetics
  • Humans
  • Imiquimod
  • Interleukin-1 Receptor-Associated Kinases / deficiency*
  • Interleukin-8 / metabolism
  • Microbial Viability / genetics
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Neutrophils / pathology
  • Oligodeoxyribonucleotides / pharmacology
  • Reactive Oxygen Species / metabolism
  • Respiratory Burst / drug effects
  • Respiratory Burst / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / pathogenicity
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Aminoquinolines
  • CPG-oligonucleotide
  • Interleukin-8
  • Oligodeoxyribonucleotides
  • Reactive Oxygen Species
  • TICAM1 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Interleukin-1 Receptor-Associated Kinases
  • Imiquimod