Stimulation of innate immune resistance leads to clearance of C. neoformans infection in zebrafish \n
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Cryptococcus neoformans is an opportunistic pathogen and a leading cause of life-threatening fungal infections in the immunocompromised.Individuals that are at greater risk are those with defective T-cell mediated immunity such as those with HIV/AIDS.Despite treatment with anti-fungal drugs, mortality remains excessively high and patients experience serious side effects hence the need to explore new therapeutic strategies.Activation of macrophages is essential for the control of cryptococcal infection.However, in the absence of T-cell mediated immunity, activation of macrophages is disrupted and clearance of cryptococcal infection is abrogated.Herein I first report a zebrafish-C.neoformans model of infection and show that zebrafish can clear, control or fail to control cryptococcal infection.I then go on to test whether cytokines or PRR ligands are capable of stimulating innate immune resistance to C. neoformans in zebrafish.I demonstrate that concomitant injection of IFN with C. neoformans results in reduced fungal burden and increased fungal clearance.IFN increases the recruitment of phagocytes to the site of infection and enhances phagocytosis by macrophages.Macrophage deficient larvae fail to clear or suppress cryptococcal infection despite treatment with IFN.In addition, infected macrophages display low lysosomal pH and elevated expression of IL-1 in IFN-treated larvae.Although neutrophils take up the fungus, their depletion does not alter cryptococcal burden.Secondly, I demonstrate that S. aureus CWP is a potent inducer of innate defences against C. neoformans.Using chemically digested S. aureus CWP to remove wall teichoic acid or mutants that do not produce wall teichoic acid (tarO) or lipoproteins (lgt), I establish that protective effects of S. aureus CWP require wall teichoic acid but not lipoproteins.Protection by S. aureus CWP are associated with increased recruitment of macrophages but not enhanced phagocytosis or TNF expression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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