Leishmania mexicana centrin knockout parasites promote M1-polarizing metabolic changes
Bibliographic record
Abstract
Leishmaniasis is a tropical disease prevalent in 90 countries. Presently, there is no approved vaccine for human use. We developed a live attenuated L. mexicana Cen −/− (LmexCen −/− ) strain as a vaccine candidate that showed excellent efficacy, characterized by reduced Th2 and enhanced Th1 responses in C57BL/6 and BALB/c mice, respectively, compared to wild-type L. mexicana (Lmex WT ) infection. Toward understanding the immune mechanisms of protection, we applied untargeted mass spectrometric analysis to LmexCen −/− and Lmex WT infections. Data showed enrichment of the pentose phosphate pathway (PPP) in ears immunized with LmexCen −/− versus naive and Lmex WT infection. PPP promotes M1 polarization in macrophages, suggesting a switch to a pro-inflammatory phenotype following LmexCen −/− inoculation. Accordingly, PPP inhibition in macrophages infected with LmexCen −/− reduced the production of nitric oxide and interleukin (IL)-1β, hallmarks of classical activation. Overall, our study revealed the immune regulatory mechanisms that may be critical for the induction of protective immunity.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| 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 | 0.001 |
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".