<i>Leishmania donovani</i> metacyclic promastigotes colonize inflammatory monocytes by impairing phagosome function
Bibliographic record
Abstract
Abstract Protozoan parasites of the Leishmania genus are the etiological agents of leishmaniasis, a debilitating disease with a wide spectrum of clinical symptoms ranging from self-healing ulcers to life-threatening visceral pathologies. These vacuolar pathogens are transmitted to mammalian hosts as metacyclic promastigotes by the bite of an infected sandfly. Parasites are then internalized by various phagocyte populations such as inflammatory monocytes. The nature of Leishmania-monocyte interactions over the course of infection and the specific role of these cells in pathogenesis are still unclear. Here, we aimed to investigate the impact of Leishmania donovani metacyclic promastigotes on inflammatory monocyte antimicrobial responses. Our results first show that these cells are highly permissive to L. donovani infection, while bacteria are rapidly eliminated. Upon internalization, L. donovani promastigotes inhibit phagosome acidification, as detected by confocal microscopy using the acidotropic probe LysoTracker. Furthermore, these parasites inhibit NOX2 assembly at the parasitophorous vacuole. Indeed, we found that the membrane-bound subunit gp91phox and the cytosolic subunit p47phox are excluded from the PV membrane. As a result, L. donovani metacyclic promastigotes prevent the production of reactive oxygen species within the PV, as detected using NitroBlue Tetrazolium. Permissiveness of inflammatory monocytes to L. donovani may thus be related to the ability of this parasite to impair the microbicidal properties of phagosomes. The virulence factors involved in these processes are currently being investigated.
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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) | 0.002 | 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".