Toll-like receptor responses in IRAK-4-deficient neutrophils.
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.
van Bruggen
Robin
R
Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.vanbruggen @ sanquin.nl
Drewniak
Agata
A
Tool
Anton T J
AT
Jansen
Machiel
M
van Houdt
Michel
M
Geissler
Judy
J
van den Berg
Timo K
TK
Chapel
Helen
H
Kuijpers
Taco W
TW
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000077271:Imiquimod; D053592:Interleukin-1 Receptor-Associated Kinases / Q000172:deficiency*; D016209:Interleukin-8 / Q000378:metabolism; D050296:Microbial Viability / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D000634:Aminoquinolines; C408982:CPG-oligonucleotide; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; D017382:Reactive Oxygen Species; C470409:TICAM1 protein, human; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D053592:Interleukin-1 Receptor-Associated Kinases; D000077271:Imiquimod