Glutathione primes β-glucan-trained immunity

Two 2021 papers on glutathione interactions with β-glucan, with the first studying human cells from healthy donors:

“(1→3)-β-D-Glucan stimulation induces epigenetic and transcriptomic changes in monocytes associated with increased glutathione (GSH) synthesis and metabolism. Intracellular glutathione levels were crucial in regulating several monocyte antifungal functions including resilience to oxidative stress, immunometabolism, nitric oxide production, phagocytosis, and cytokine production.

Our findings demonstrate an important role for GSH in immunity, and outline a better understanding of the acute response of monocytes to infections.” “Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-β-D-Glucan”

A second study investigated the subject with a dozen rodent experiments:

“We demonstrated that antioxidation by GSH supported an environment essential for β-glucan-induced metabolic and epigenetic changes in monocytes. We found that GSH induced glycolysis and glutaminolysis in β-glucan-trained immunity in a mTOR-dependent manner.

These results uncovered the GSH/mTOR/c-Myc signaling axis as the central effector of metabolic reprogramming in trained immunity. We revealed that the delicate GSH/ROS redox balance determines discrete, long lasting metabolic modifications that are causal to β-glucan-trained immunity.

Our results suggest that H3K27me3 demethylation is a necessary event. We identified H3K27me3 demethylation as a novel histone modification mark that was impaired by GSH deficiency in β-glucan-trained bone marrow derived macrophages.

We identified EZH2 as a potential tool to boost trained immunity under GSH deficiency conditions, or to enhance trained immunity in clinical settings where excessive inflammatory responses could be beneficial.

ezh2 survival

Overall, these insights contribute to unraveling metabolic and epigenetic changes during trained immunity.” “Glutathione synthesis primes monocytes metabolic and epigenetic pathway for β-glucan-trained immunity”

The second paper of Remembering encounters provides future benefits also explored this subject.


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