TLR signaling and effector functions are intact in XLA neutrophils.
Toll-like receptors (TLRs) are essential components of the innate immune system, and their ligands are important activators of neutrophils. Bruton's tyrosine kinase (Btk) has been reported to mediate signaling through toll-like receptors (TLRs) in many cell types, however, the role of Btk in TLR activation of neutrophils remains unclear. Impaired TLR-induced neutrophil function was found in mice with loss of Btk and in humans with TLR-signaling defects, but the integrity of TLR pathways in X-linked agammaglobulinemia (XLA) neutrophils has not been assessed. In this study LPS (TLR4) or an imidazoquinoline compound (TLR7/8) activated XLA neutrophil shedding of surface CD62L, and phosphorylated MAP kinases p38, JNK and ERK. TLR activation also induced normal respiratory burst and retarded apoptosis for XLA neutrophils, comparable to normal controls. These data demonstrate that the loss of Btk in XLA neutrophils does not impair functional responses to TLR signals.
Marron
Thomas U
TU
Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA.
Rohr
Kaileen
K
Martinez-Gallo
Monica
M
Yu
Joyce
J
Cunningham-Rundles
Charlotte
C
D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002648:Child; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019041:L-Selectin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists*; D055815:Young Adult
C547051:CL097 compound; D007093:Imidazoles; D008070:Lipopolysaccharides; D011804:Quinolines; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D019041:L-Selectin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate