Virus-associated Inflammation Imprints an Inflammatory Profile on Long-lived Monocyte-derived Macrophages in the Human Liver
Bibliographic record
Abstract
Abstract Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating in an inflammatory environment can potentially imprint a phenotype that switches the liver from an immunotolerant organ to one predisposed to tissue damage. We longitudinally sampled the liver of chronic hepatitis B (CHB) patients with active liver inflammation starting antiviral therapy. Antiviral therapy suppressed viral replication and liver inflammation, which coincided with decreased myeloid activation markers. Single-cell RNA sequencing mapped peripheral inflammatory markers to a monocyte-derived macrophage population, distinct from Kupffer cells, with an inflammatory transcriptional profile. The inflammatory macrophages (iMacs) differentiated from blood monocytes and established a long-lived population. The iMacs retained their core transcriptional signature, consistent with trained immunity, resulting in a population of macrophages primed for inflammation potentially driving progressive liver disease.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".