Open AccessToll-Like Receptor Responses in IRAK-4-Deficient Neutrophils
Author(s) -
Robin van Bruggen,
Agata Drewniak,
Anton T.J. Tool,
Machiel H. Jansen,
Michel van Houdt,
Judy Geissler,
Timo K. van den Berg,
Helen Chapel,
Taco W. Kuijpers
Publication year - 2009
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000268288
Subject(s) - trif , chemotaxis , toll like receptor , microbiology and biotechnology , receptor , candida albicans , tlr4 , innate immune system , biology , tlr7 , tlr3 , staphylococcus aureus , secretion , chemistry , immunology , inflammation , bacteria , biochemistry , genetics
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.