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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8947638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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