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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/6/1003 |
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| author | Vincenzo Nasillo Ivana Lagreca Daniela Vallerini Patrizia Barozzi Giovanni Riva Monica Maccaferri Ambra Paolini Fabio Forghieri Stefania Fiorcari Rossana Maffei Silvia Martinelli Claudio Giacinto Atene Ilaria Castelli Roberto Marasca Leonardo Potenza Patrizia Comoli Rossella Manfredini Enrico Tagliafico Tommaso Trenti Mario Luppi |
| author_facet | Vincenzo Nasillo Ivana Lagreca Daniela Vallerini Patrizia Barozzi Giovanni Riva Monica Maccaferri Ambra Paolini Fabio Forghieri Stefania Fiorcari Rossana Maffei Silvia Martinelli Claudio Giacinto Atene Ilaria Castelli Roberto Marasca Leonardo Potenza Patrizia Comoli Rossella Manfredini Enrico Tagliafico Tommaso Trenti Mario Luppi |
| author_sort | Vincenzo Nasillo |
| collection | DOAJ |
| 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 <i>Aspergillus fumigatus</i>, 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. |
| first_indexed | 2024-03-09T20:01:19Z |
| format | Article |
| id | doaj.art-ca4af20392324702a25ff5681c822087 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:01:19Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ca4af20392324702a25ff5681c8220872023-11-24T00:44:29ZengMDPI AGCells2073-44092022-03-01116100310.3390/cells11061003BTK Inhibitors Impair Platelet-Mediated Antifungal ActivityVincenzo Nasillo0Ivana Lagreca1Daniela Vallerini2Patrizia Barozzi3Giovanni Riva4Monica Maccaferri5Ambra Paolini6Fabio Forghieri7Stefania Fiorcari8Rossana Maffei9Silvia Martinelli10Claudio Giacinto Atene11Ilaria Castelli12Roberto Marasca13Leonardo Potenza14Patrizia Comoli15Rossella Manfredini16Enrico Tagliafico17Tommaso Trenti18Mario Luppi19Diagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, AUSL/AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalyDiagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, AUSL/AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalyPediatric Hematology/Oncology Unit and Cell Factory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, 27100 Pavia, ItalyCentre for Regenerative Medicine “S. Ferrari”, University of Modena and Reggio Emilia, 41125 Modena, ItalyDiagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, AUSL/AOU Modena, 41124 Modena, ItalyDiagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, AUSL/AOU Modena, 41124 Modena, ItalySection of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, ItalyIn 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 <i>Aspergillus fumigatus</i>, 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.https://www.mdpi.com/2073-4409/11/6/1003BTK inhibitorsplateletsibrutinibacalabrutinibCLLinvasive fungal infections |
| spellingShingle | Vincenzo Nasillo Ivana Lagreca Daniela Vallerini Patrizia Barozzi Giovanni Riva Monica Maccaferri Ambra Paolini Fabio Forghieri Stefania Fiorcari Rossana Maffei Silvia Martinelli Claudio Giacinto Atene Ilaria Castelli Roberto Marasca Leonardo Potenza Patrizia Comoli Rossella Manfredini Enrico Tagliafico Tommaso Trenti Mario Luppi BTK Inhibitors Impair Platelet-Mediated Antifungal Activity Cells BTK inhibitors platelets ibrutinib acalabrutinib CLL invasive fungal infections |
| 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 | BTK inhibitors platelets ibrutinib acalabrutinib CLL invasive fungal infections |
| url | https://www.mdpi.com/2073-4409/11/6/1003 |
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