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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 publication

DOI

10.1159/000268288

Type

Journal article

Journal

J Innate Immun

Publication Date

2010

Volume

2

Pages

280 - 287

Keywords

Adaptor Proteins, Vesicular Transport, Aminoquinolines, Bacterial Infections, Candida albicans, Candidiasis, Cell Adhesion, Cells, Cultured, Chemotaxis, Humans, Interleukin-1 Receptor-Associated Kinases, Interleukin-8, Microbial Viability, Neutrophils, Oligodeoxyribonucleotides, Reactive Oxygen Species, Respiratory Burst, Signal Transduction, Staphylococcus aureus, Toll-Like Receptor 3, Toll-Like Receptor 7