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Series GSE243974 Query DataSets for GSE243974
Status Public on May 17, 2024
Title BTK drives neutrophil activation for sterilizing antifungal immunity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary We describe a previously unappreciated role for Bruton's tyrosine kinase (BTK) in fungal immune surveillance against aspergillosis, an unforeseen complication of BTK inhibitors (BTKi) used for treating B-cell lymphoid malignancies. We studied BTK-dependent fungal responses in neutrophils from diverse populations, including healthy donors, BTKi-treated patients, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcgR-dependent manner, triggering the oxidative burst. BTK inhibition selectively impeded neutrophil-mediated damage to Aspergillus hyphae, primary granule release, and the fungus-induced oxidative burst by abrogating NADPH oxidase subunit p40phox and GTPase RAC2 activation. Moreover, neutrophil-specific Btk deletion in mice enhanced aspergillosis susceptibility by impairing neutrophil function, not recruitment nor lifespan. Conversely, GM-CSF partially mitigated these deficits by enhancing p47phox activation. Our findings underline the crucial role of BTK signaling in neutrophils for antifungal immunity and provide a rationale for GM-CSF use to offset these deficits in susceptible patients.
 
Overall design Peripheral blood was drawn and neutrophils purified using negative selection (StemCell Technologies).
 
Contributor(s) Wigerblad G, Brooks S, Desai J, Lionakis M
Citation(s) 38696257
Submission date Sep 25, 2023
Last update date May 18, 2024
Contact name Gustaf Wigerblad
E-mail(s) gustaf.wigerblad@nih.gov
Organization name National Institutes of Health
Department NIAMS
Street address 10 Center Dr
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (6)
GSM7802635 Cancer1_Neu_pre
GSM7802636 Cancer2_Neu_pre
GSM7802637 Cancer3_Neu_pre
Relations
BioProject PRJNA1020829

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE243974_RAW.tar 267.3 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA

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