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BTK Inhibitors Impair Platelet-Mediated Antifungal Activity
- Source :
- Cells; Volume 11; Issue 6; Pages: 1003
- Publication Year :
- 2022
-
Abstract
- 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.
- Subjects :
- Acalabrutinib
Aspergillus
BTK inhibitors
CLL
Ibrutinib
Invasive fungal infections
Molds
Platelets
Agammaglobulinaemia Tyrosine Kinase
Antifungal Agents
Blood Platelets
Humans
Protein Kinase Inhibitors
Aspergillosis
Invasive Fungal Infections
Leukemia, Lymphocytic, Chronic, B-Cell
platelets
ibrutinib
acalabrutinib
invasive fungal infections
molds
Leukemia
B-Cell
General Medicine
Lymphocytic
Chronic
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 11
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....d1b3b7e1e6d129a27dce4d51368bbbcc