<i>Leishmania mexicana Centrin</i> Knock out Parasites Promote M1-polarizing Metabolic Changes
Bibliographic record
Abstract
ABSTRACT Leishmaniasis is a tropical disease present in more than 90 countries. Presently, there is no approved vaccine for human use. We have previously developed live attenuated L. mexicana Cen −/− (LmexCen −/− ) as a vaccine candidate that showed excellent efficacy that was characterized by reduced activation of Th2 responses and enhanced Th1 responses, contrary to wild type L. mexicana (Lmex WT ) infection. Towards understanding the interplay between immune mechanisms of protection and metabolic reprogramming, we applied untargeted mass spectrometric analysis to LmexCen −/− and compared them with Lmex WT infection. Data showed that enriched pentose phosphate pathway (PPP) in ears immunized with LmexCen −/− parasites, compared to naïve and Lmex WT-infected ears. This pathway is known to promote an M1 phenotype in macrophages, suggesting a switch to a pro-inflammatory phenotype following LmexCen −/− inoculation. Accordingly, inhibition of the PPP in macrophages cultured with LmexCen −/− parasites led to diminished production of nitric oxide, IL-12, and IL-1β, hallmarks of classical activation. Overall, our study revealed novel immune regulatory mechanisms that may be critical for the induction of protective immunity.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".