Recombinant<i>Leishmania major</i>Secreting Biologically Active Granulocyte-Macrophage Colony-Stimulating Factor Survives Poorly in Macrophages In Vitro and Delays Disease Development in Mice
Bibliographic record
Abstract
Leishmania is an intracellular pathogen that replicates inside macrophages. Activated macrophages produce a specific subset of cytokines that play an important role in the control of Leishmania infections. As part of our interest in developing suicide parasites that produce abortive infections for the purposes of vaccination, we engineered recombinant Leishmania major strains producing biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF). We showed that GM-CSF is being produced in the phagosomes of infected macrophages and that it can be detected in the culture supernatants of both infected macrophages and extracellular parasites. Our data support the notion that GM-CSF secreted by both developmental forms of recombinant L. major can activate macrophages to produce high levels of proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, and IL-18 and various chemokines including RANTES/CCL5, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2, and MCP-1/CCL2, which enhance parasite killing. Indeed, GM-CSF-expressing parasites survive poorly in macrophages in vitro and produce delayed lesion development in susceptible BALB/c mice in vivo. Selective killing of intracellular Leishmania expressing cytokine genes capable of activating cellular responses may constitute a promising strategy to control and/or prevent parasitic infections.
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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 | 0.000 |
| 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 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".