Jigar V Desai, Marissa A Zarakas, Andrew L Wishart, Mark Roschewski, Mariano A Aufiero, Ágnes Donkó, Gustaf Wigerblad, Neta Shlezinger, Markus Plate, Matthew R James, Jean K Lim, Gulbu Uzel, Jenna Re Bergerson, Ivan Fuss, Robert A Cramer, Luis M Franco, Emily S Clark, Wasif N Khan, Daisuke Yamanaka, Georgios Chamilos, Jamel El-Benna, Mariana J Kaplan, Louis M Staudt, Thomas L Leto, Steven M Holland, Wyndham H Wilson, Tobias M Hohl, Michail S Lionakis
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 FcγR-dependent manner, triggering the oxidative burst...
May 2, 2024: Journal of Clinical Investigation