Decreased Cell Wall Galactosaminogalactan in <i>Aspergillus nidulans</i> Mediates Dysregulated Inflammation in the Chronic Granulomatous Disease Host
Why this work is in the frame
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Bibliographic record
Abstract
Invasive aspergillosis is a major threat to patients suffering from impaired neutrophil function, with Aspergillus fumigatus being the most common species causing this life-threatening condition. Patients with chronic granulomatous disease (CGD) not only develop infections with A. fumigatus, but also exhibit a unique susceptibility to infection with the normally nonpathogenic species Aspergillus nidulans. In this study, we compared the inflammatory cytokine response of peripheral blood mononuclear cells (PBMCs) from healthy and CGD patients to these two fungal species. CGD patients displayed evidence for a chronic hyperinflammatory state as indicated by elevated plasma IL-1β and TNF-α levels. PBMCs isolated from CGD patients secreted higher levels of IL-1β and TNF-α in response to A. nidulans as compared with A. fumigatus. The presence or absence of melanin in the cell wall of A. nidulans did not alter the cytokine release by healthy or CGD PBMCs. In contrast, A. fumigatus mutants lacking melanin stimulated higher levels of proinflammatory cytokine release from healthy, but not CGD PBMCs. Purified cell wall polysaccharides of A. nidulans induced a much higher level of IL-1β secretion by CGD PBMCs than did cell wall polysaccharides isolated from A. fumigatus. Using modified A. nidulans strains overexpressing galactosaminogalactan, we were able to show that the increased secretion of inflammatory cytokines by CGD PBMCs in response to A. nidulans are a consequence of low levels of cell wall-associated galactosaminogalactan in this species.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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