Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-β-D-Glucan
Why this work is in the frame
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Bibliographic record
Abstract
(1→3)-β-D-Glucan (BDG) represents a potent pathogen-associated molecular pattern (PAMP) in triggering the host response to fungal and some bacterial infections. Monocytes play a key role in recognizing BDG and governing the acute host response to infections. However, the mechanisms regulating monocyte's acute response to BDG are poorly understood. We sought to investigate the response of monocytes to BDG at the epigenetic, transcriptomic, and molecular levels. Response of human monocytes to 1, 4, and 24 hours of BDG exposure was investigated using RNA-seq, ATAC-seq, H3K27ac and H3K4me1 ChIP-seq. We show that pathways including glutathione metabolism, pentose phosphate pathway, and citric acid cycle were upregulated at the epigenetic and transcriptomic levels in response to BDG exposure. Strikingly, unlike bacterial lipopolysaccharides, BDG induced intracellular glutathione synthesis. BDG exposure also induced NADP synthesis, increased NADPH/NADP ratio, and increased expression of genes involved in the pentose phosphate pathway in a GSH-dependent manner. By inhibiting GSH synthesis with L-buthionine sulfoximine (BSO) before BDG exposure we show that the GSH pathway promotes cell survival and regulates monocyte's effector functions including NO production, phagocytosis, and cytokine production. In summary, our work demonstrates that BDG induces glutathione synthesis and metabolism in monocytes, which is a major promoter of the acute functional response of monocytes to infections.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it