1. Chronic ethanol exposure decreases H3K27me3 in the Il6 promoter region of macrophages and generates persistent dysfunction on neutrophils during fungal infection.
- Author
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Martins FRB, Beltrami VA, Zenóbio IC, Martins DG, da Silva Gurgel IL, de Assis Rabelo Ribeiro N, Queiroz-Junior CM, Bonaventura D, Rezende BM, Teixeira MM, Pinho V, Oliveira NL, and Soriani FM
- Subjects
- Animals, Mice, Inbred C57BL, Male, Lung immunology, Lung drug effects, Lung pathology, Mice, Chemokine CXCL2 genetics, Chemokine CXCL2 metabolism, Phagocytosis drug effects, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Ethanol, Interleukin-6 genetics, Interleukin-6 metabolism, Neutrophils immunology, Neutrophils drug effects, Promoter Regions, Genetic, Aspergillus fumigatus, Macrophages drug effects, Macrophages immunology, Histones metabolism, Aspergillosis immunology
- Abstract
Objective and Design: The aim of this study was to investigate the effects of ethanol exposure on epigenetic markers in bone marrow (BM) and their impact on inflammatory response during Aspergillus fumigatus infection., Results: Chronic ethanol exposure decreased H3K27me3 enrichment in the Il6 promoter region while increased H3K4me3 enrichment in Tnf. Chimeric mice were generated by transplanting BM from mice exposed to ethanol or water. Infection of ethanol-chimeric mice culminated in higher clinical scores, although there was no effect on mortality. However, previous chronic exposure to ethanol affects persistently the inflammatory response in lung tissue, demonstrated by increased lung damage, neutrophil accumulation and IL-6, TNF and CXCL2 production in ethanol-chimeric mice, resulting in a decreased neutrophil infiltration into the alveolar space. Neutrophil killing and phagocytosis were also significantly lower. Moreover, BM derived macrophages (BMDM) from ethanol-chimeric mice stimulated with A. fumigatus conidia exhibited higher levels of TNF, CXCL2 and IL-6 release and a higher killing activity. The Il6 promoter of BMDM from ethanol-chimeric mice exhibited a reduction in H3K27me3 enrichment, a finding also observed in BM donors exposed to ethanol., Conclusions: These evidences demonstrate that prior chronic alcohol exposure of bone-marrow modify immune effector cells functions impairing the inflammatory response during A. fumigatus infection. These findings highlight the persistent impact of chronic ethanol exposure on infectious disease outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Published
- 2024
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