β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
By B. Novaković, E. Habibi, Shuang-Yin Wang, R. Arts, R. Davar, Wout Megchelenbrink, Bowon Kim, T. Kuznetsova, M. Kox, J. Zwaag and 16 more. Cell, 2016
600 citations recorded by the source corpus.
Summary 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.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/7931163c48ae42443737ff19530757c0005781fb
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Citations in the corpus
- BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. (2018, methodology): “Chromatin was sonicated and immunoprecipitated using an antibody for H3K27ac (Diagenode) as described previously (Novakovic et al., 2016).”
- Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018, positive): “This is consistent with previous observation for b-glucan-trained macrophages that the major differences in gene expression are present during the first 24 hr after b-glucan stimulation, whereas at later time points transcriptional differences are less pronounced (Novakovic et al., 2016).”
- Diversity, Mechanisms and Significance of Macrophage Plasticity (2019, background): “Finally, ex vivo β-glucan treatment of monocytes from volunteers with experimental endotoxemia partially reverses ET, restoring monocytes’ capacity for cytokine production (60).”