{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:41:47Z","timestamp":1792600907728,"version":"4.5.0"},"reference-count":29,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>&lt;p&gt;Introduction: Bruton tyrosine kinase inhibitors (BTKi) impair anti-Aspergillus immune responses and increase the risk of invasive fungal infections (IFI). More selective second-generation BTKi have fewer off-target effects thus a better tolerance than ibrutinib. Though clinical data suggest the incidence of IFI is lower with second-generation BTKi, whether they have less impact on antifungal immunity remains unclear. Methods: We studied the activation phenotype and behavior of human neutrophils in vitro with fungal extracts or living Aspergillus fumigatus in the presence of either ibrutinib or zanubrutinib, a more selective second-generation BTKi, using various approaches, including live microscopy. Results: Both molecules inhibited the activation-induced phenotypic changes in neutrophils following exposure to hyphae. Similarly, ibrutinib and zanubrutinib impaired neutrophil-mediated inhibition of conidia germination. By contrast, live neutrophil imaging showed that neutrophils exposed to ibrutinib but not zanubrutinib kept a round morphology, suggesting a defective activation, were less mobile, and showed impaired conidia phagocytosis. Conclusion: We confirm here that ibrutinib and zanubrutinib inhibit neutrophil antifungal activity, strongly suggesting that BTK plays a central role. However, subtle differences between ibrutinib and zanubrutinib were evidenced using live microscopy, which might indicate additional off-target effects, and potentially partially explain the lower incidence of IFI with zanubrutinib; the clinical relevance remains to be determined.&lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/jin\/adhag001","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:05:07Z","timestamp":1786021507000},"page":"448-460","source":"Crossref","is-referenced-by-count":0,"title":["Differential Effects of Zanubrutinib and Ibrutinib on Neutrophil Antifungal Functions: Insights from Live-Cell Imaging"],"prefix":"10.1159","volume":"18","author":[{"given":"Benoit 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