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BTK Inhibitors Impair Platelet-Mediated Antifungal Activity

In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive th...

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Autores principales: Nasillo, Vincenzo, Lagreca, Ivana, Vallerini, Daniela, Barozzi, Patrizia, Riva, Giovanni, Maccaferri, Monica, Paolini, Ambra, Forghieri, Fabio, Fiorcari, Stefania, Maffei, Rossana, Martinelli, Silvia, Atene, Claudio Giacinto, Castelli, Ilaria, Marasca, Roberto, Potenza, Leonardo, Comoli, Patrizia, Manfredini, Rossella, Tagliafico, Enrico, Trenti, Tommaso, Luppi, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947638/
https://www.ncbi.nlm.nih.gov/pubmed/35326454
http://dx.doi.org/10.3390/cells11061003
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author Nasillo, Vincenzo
Lagreca, Ivana
Vallerini, Daniela
Barozzi, Patrizia
Riva, Giovanni
Maccaferri, Monica
Paolini, Ambra
Forghieri, Fabio
Fiorcari, Stefania
Maffei, Rossana
Martinelli, Silvia
Atene, Claudio Giacinto
Castelli, Ilaria
Marasca, Roberto
Potenza, Leonardo
Comoli, Patrizia
Manfredini, Rossella
Tagliafico, Enrico
Trenti, Tommaso
Luppi, Mario
author_facet Nasillo, Vincenzo
Lagreca, Ivana
Vallerini, Daniela
Barozzi, Patrizia
Riva, Giovanni
Maccaferri, Monica
Paolini, Ambra
Forghieri, Fabio
Fiorcari, Stefania
Maffei, Rossana
Martinelli, Silvia
Atene, Claudio Giacinto
Castelli, Ilaria
Marasca, Roberto
Potenza, Leonardo
Comoli, Patrizia
Manfredini, Rossella
Tagliafico, Enrico
Trenti, Tommaso
Luppi, Mario
author_sort Nasillo, Vincenzo
collection PubMed
description In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients.
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spelling pubmed-89476382022-03-25 BTK Inhibitors Impair Platelet-Mediated Antifungal Activity Nasillo, Vincenzo Lagreca, Ivana Vallerini, Daniela Barozzi, Patrizia Riva, Giovanni Maccaferri, Monica Paolini, Ambra Forghieri, Fabio Fiorcari, Stefania Maffei, Rossana Martinelli, Silvia Atene, Claudio Giacinto Castelli, Ilaria Marasca, Roberto Potenza, Leonardo Comoli, Patrizia Manfredini, Rossella Tagliafico, Enrico Trenti, Tommaso Luppi, Mario Cells Article In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients. MDPI 2022-03-16 /pmc/articles/PMC8947638/ /pubmed/35326454 http://dx.doi.org/10.3390/cells11061003 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nasillo, Vincenzo
Lagreca, Ivana
Vallerini, Daniela
Barozzi, Patrizia
Riva, Giovanni
Maccaferri, Monica
Paolini, Ambra
Forghieri, Fabio
Fiorcari, Stefania
Maffei, Rossana
Martinelli, Silvia
Atene, Claudio Giacinto
Castelli, Ilaria
Marasca, Roberto
Potenza, Leonardo
Comoli, Patrizia
Manfredini, Rossella
Tagliafico, Enrico
Trenti, Tommaso
Luppi, Mario
BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title_full BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title_fullStr BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title_full_unstemmed BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title_short BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
title_sort btk inhibitors impair platelet-mediated antifungal activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947638/
https://www.ncbi.nlm.nih.gov/pubmed/35326454
http://dx.doi.org/10.3390/cells11061003
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