{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:44:21Z","timestamp":1791841461333,"version":"4.3.4"},"reference-count":105,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["ZIA AI001175"],"award-info":[{"award-number":["ZIA AI001175"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,17]]},"abstract":"<jats:p>\n                    We describe a previously unappreciated role for Bruton\u2019s 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 Fc\u03b3R-dependent manner, triggering the oxidative burst. BTK inhibition selectively impeded neutrophil-mediated damage to\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    hyphae, primary granule release, and the fungus-induced oxidative burst by abrogating NADPH oxidase subunit p40\n                    <jats:sup>phox<\/jats:sup>\n                    and GTPase RAC2 activation. Moreover, neutrophil-specific\n                    <jats:italic>Btk<\/jats:italic>\n                    deletion in mice enhanced aspergillosis susceptibility by impairing neutrophil function, not recruitment or lifespan. Conversely, GM-CSF partially mitigated these deficits by enhancing p47\n                    <jats:sup>phox<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1172\/jci176142","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T03:18:53Z","timestamp":1714792733000},"source":"Crossref","is-referenced-by-count":37,"title":["BTK drives neutrophil activation for sterilizing antifungal immunity"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8823-0796","authenticated-orcid":true,"given":"Jigar V.","family":"Desai","sequence":"first","affiliation":[{"name":"Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology (LCIM), National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa A.","family":"Zarakas","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology (LCIM), National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Wishart","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology (LCIM), National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Roschewski","sequence":"additional","affiliation":[{"name":"Lymphoid Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano A.","family":"Aufiero","sequence":"additional","affiliation":[{"name":"Louis V. 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