Transcriptional Profiling Suggests Extensive Metabolic Rewiring of Human and Mouse Macrophages during Early Interferon Alpha Responses
Why this work is in the frame
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Bibliographic record
Abstract
Emerging evidence suggests that cellular metabolism plays a critical role in regulating immune activation. Alterations in energy and lipid and amino acid metabolism have been shown to contribute to type I interferon (IFN) responses in macrophages, but the relationship between metabolic reprogramming and the establishment of early antiviral function remains poorly defined. Here, we used transcriptional profiling datasets to develop global metabolic signatures associated with early IFN- α responses in two primary macrophage model systems: mouse bone marrow-derived macrophages (BMM) and human monocyte-derived macrophages (MDM). Short-term stimulation with IFN- α (<4 hours) was associated with significant metabolic rewiring, with >500 metabolic genes altered in mouse and human macrophage models. Pathway and network analysis identified alterations in genes associated with cellular bioenergetics, cellular oxidant status, cAMP/AMP and cGMP/GMP ratios, branched chain amino acid catabolism, cell membrane composition, fatty acid synthesis, and β -oxidation as key features of early IFN- α responses. These changes may have important implications for initial establishment of antiviral function in these cells.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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