ArticleJournal of innate immunity2026
Differential Effects of Zanubrutinib and Ibrutinib on Neutrophil Antifungal Functions: Insights from Live-Cell Imaging.
Article in Journal of innate immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionBruton 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.
methodsWe 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.
resultsBoth 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.
conclusionWe 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.
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