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

Robin van Bruggen, Agata Drewniak, Anton T J Tool, Machiel Jansen, Michel van Houdt, Judy Geissler, Timo K van den Berg, Helen Chapel, Taco W Kuijpers

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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.

Original languageEnglish
Pages (from-to)280-7
Number of pages8
JournalJournal of innate immunity
Issue number3
Publication statusPublished - 2010


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

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