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β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance.
- Source :
-
Cell [Cell] 2016 Nov 17; Vol. 167 (5), pp. 1354-1368.e14. - Publication Year :
- 2016
-
Abstract
- Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, β-glucan partially reverses the LPS-induced tolerance in vitro. Importantly, ex vivo β-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes. VIDEO ABSTRACT.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Differentiation
DNA Methylation
Epigenomics
Gene Regulatory Networks
Histone Code
Humans
Immunity, Innate
Immunologic Memory
Macrophages cytology
Monocytes cytology
Sepsis genetics
Immune Tolerance
Lipopolysaccharides immunology
Macrophages immunology
Monocytes immunology
Sepsis immunology
Transcription, Genetic
beta-Glucans immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 167
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 27863248
- Full Text :
- https://doi.org/10.1016/j.cell.2016.09.034