{"doi":"10.1172/jci176142","title":"BTK drives neutrophil activation for sterilizing antifungal immunity","abstract":"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, patients who were treated with BTKi, and X-linked agammaglobulinemia patients. Upon fungal exposure, BTK was activated in human neutrophils in a TLR2-, Dectin-1-, and FcγR-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 or 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 patients who are susceptible.","journal":"Journal of Clinical Investigation","year":2024,"id":421582,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9628,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":531349,"name":"Marissa A. Zarakas","orcid":null,"position":1,"is_corresponding":false},{"id":248010,"name":"Andrew Wishart","orcid":"0000-0002-2531-6349","position":2,"is_corresponding":false},{"id":233601,"name":"Mark Roschewski","orcid":"0000-0003-0278-2635","position":3,"is_corresponding":false},{"id":288397,"name":"Mariano A. Aufiero","orcid":"0000-0003-2462-438X","position":4,"is_corresponding":false},{"id":1215114,"name":"Ágnes Donkó","orcid":null,"position":5,"is_corresponding":false},{"id":218254,"name":"Gustaf Wigerblad","orcid":"0000-0002-1798-4347","position":6,"is_corresponding":false},{"id":721662,"name":"Neta Shlezinger","orcid":"0000-0001-7448-5846","position":7,"is_corresponding":false},{"id":1215115,"name":"Markus Plate","orcid":null,"position":8,"is_corresponding":false},{"id":997483,"name":"M R James","orcid":"0000-0002-8548-5080","position":9,"is_corresponding":false},{"id":103719,"name":"Jean K. Lim","orcid":"0000-0002-4572-6417","position":10,"is_corresponding":false},{"id":295452,"name":"Gülbû Uzel","orcid":"0000-0002-3942-1086","position":11,"is_corresponding":false},{"id":266867,"name":"Jenna Bergerson","orcid":"0000-0001-9122-4998","position":12,"is_corresponding":false},{"id":278165,"name":"Ivan J. Fuss","orcid":"0000-0002-1278-2340","position":13,"is_corresponding":false},{"id":258383,"name":"Robert A. Cramer","orcid":"0000-0001-5503-5006","position":14,"is_corresponding":false},{"id":282812,"name":"Luis M. Franco","orcid":"0000-0002-0540-5942","position":15,"is_corresponding":false},{"id":733114,"name":"Emily S. Clark","orcid":null,"position":16,"is_corresponding":false},{"id":732353,"name":"Wasif N. Khan","orcid":"0000-0002-7354-8312","position":17,"is_corresponding":false},{"id":365102,"name":"Daisuke Yamanaka","orcid":"0000-0002-0046-7052","position":18,"is_corresponding":false},{"id":491993,"name":"Georgios Chamilos","orcid":"0000-0002-7987-4055","position":19,"is_corresponding":false},{"id":670964,"name":"Jamel El‐Benna","orcid":"0000-0001-5733-216X","position":20,"is_corresponding":false},{"id":218262,"name":"Mariana J. Kaplan","orcid":"0000-0003-2968-0815","position":21,"is_corresponding":false},{"id":35688,"name":"Louis M. Staudt","orcid":"0000-0002-1735-2892","position":22,"is_corresponding":false},{"id":738266,"name":"Thomas L. Leto","orcid":"0000-0002-5463-1583","position":23,"is_corresponding":false},{"id":104227,"name":"Steven M. Holland","orcid":"0000-0003-3207-5464","position":24,"is_corresponding":false},{"id":35694,"name":"Wyndham H. Wilson","orcid":"0000-0002-2862-9711","position":25,"is_corresponding":false},{"id":228380,"name":"Tobias M. Hohl","orcid":"0000-0002-9097-5412","position":26,"is_corresponding":false},{"id":104225,"name":"Michail S. Lionakis","orcid":"0000-0003-4994-9500","position":27,"is_corresponding":false},{"id":231233,"name":"Jigar V. Desai","orcid":"0000-0002-8823-0796","position":0,"is_corresponding":true}],"reference_count":110,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:41.370244Z","pmid":"38696257","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}