Abstract Fri024: Monocyte-Derived Macrophages Prevent the Development of Viral Cardiomyopathy during Viral Myocarditis
Bibliographic record
Abstract
Background: Viral myocarditis – inflammation of the heart caused by viral infection – is an underappreciated yet critical contributor to heart failure. While some patients fully recover, others progress to viral cardiomyopathy, but the underlying mechanisms driving this divergence remain unclear. Macrophages are a heterogenous population of immune cells in the heart comprising embryonic versus monocyte derived subsets with both cardioprotective and pathological functions depending on context (disease, origin). However, the dynamics and function of macrophages during viral myocarditis has never been investigated. Research Question: We tested the hypothesis that monocyte-derived macrophages are cardioprotective during viral myocarditis by promoting anti-viral and reparative pathways. Approach: We model viral myocarditis in mice using the cardiotropic virus encephalomyocarditis virus variant D (EMCV-D). CCR2 is a chemokine required for monocyte egress from the bone-marrow. CCR2-knockout (CCR2-KO) mice lack monocyte recruitment to the heart and were used to study the function of this subset. Results: CCR2+ monocyte-derived macrophages were the dominant immune cell recruited to the heart during myocarditis, while embryonic-derived macrophages were diminished. The lack of monocyte recruitment to the heart in CCR2-KO mice resulted in the development of cardiac dysfunction (2-fold reduction in left ventricular ejection fraction, p<0.05, n=15-20/group) and increased cardiac fibrosis (5-fold increase, p<0.001, n=15-20/group). CCR2-KO mice had exaggerated neutrophil recruitment, reduced natural killer cells and reduced virus-specific CD8+ T cells within the heart, suggesting reduced virus “killing” and clearance (p<0.001, n=15-20/group). Spatial transcriptomics (10x Visium) analyses demonstrated that CCR2+ macrophages localized within focal inflammatory lesions near cardiomyocytes, fibroblasts and T cells. In CCR2-KO mice, inflammatory lesions were comprised of neutrophils, myofibroblasts and stressed cardiomyocytes, suggesting that spatial patterns of altered immune and stromal responses may underly distinct pathological outcomes in monocyte deficient mice. Conclusion: Therefore, these data highlight a novel cardioprotective role for CCR2+ monocyte-derived macrophages during viral myocarditis, with implications for precise, targeted therapies for viral cardiomyopathy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 source (direct Gemma or distilled Codex), 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".