Bromodomain inhibitor I-BET151 suppresses immune responses during fungal-immune interaction.

Abstract:

:Changes in the epigenetic landscape of immune cells are a crucial component of gene activation during the induction of inflammatory responses, therefore it has been hypothesized that epigenetic modulation could be employed to restore homeostasis in inflammatory scenarios. Fungal pathogens cause a large burden of morbidity and even mortality due to the hyperinflammatory processes that induce mucosal, allergic or systemic infections. Bromodomain and extraterminal domain (BET) proteins are considered as one as the most tantalizing pharmacological targets for the modulation of inflammatory responses at the epigenetic level. Nothing is known of the role of BET inhibitors on the inflammation induced by fungal pathogens. In the present study, we assessed the in vitro efficacy of the small molecular histone mimic BET inhibitor I-BET151 to modulate innate immune responses during fungal-immune interaction with the clinically relevant fungal pathogens Candida albicans and Aspergillus fumigatus. Our results prove that BET inhibitors (I-BETs) represent an important modulator of inflammation induced by fungal pathogens: both direct production of proinflammatory cytokines and the induction of trained immunity were inhibited by I-BET151. These modulatory effects are likely to have important potential implications in clinically relevant situations.

journal_name

Eur J Immunol

authors

Domínguez-Andrés J,Ferreira AV,Jansen T,Smithers N,Prinjha RK,Furze RC,Netea MG

doi

10.1002/eji.201848081

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

2044-2050

issue

11

eissn

0014-2980

issn

1521-4141

journal_volume

49

pub_type

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