Leishmania donovani promastigotes induce periphagosomal F-actin accumulation through retention of the GTPase Cdc42
Why this work is in the frame
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Bibliographic record
Abstract
Leishmania donovani promastigotes inhibit phagosome maturation and induce the accumulation of periphagosomal F-actin during the establishment of infection within macrophages. These events are mediated by the surface glycolipid lipophosphoglycan (LPG), but the underlying mechanisms remain to be elucidated. In this study, we addressed the role of the Rho-family GTPases RhoA, Rac1 and Cdc42 in the uptake of L. donovani promastigotes and in the accumulation of periphagosomal F-actin. Confocal microscopy analyses revealed that association of both Rac1 and RhoA to phagosomes containing L. donovani promastigotes was independent of the presence of LPG. In contrast, Cdc42 and proteins required for F-actin assembly (Arp2/3, WASP, Myosin, alpha-actinin) were retained on phagosomes in a LPG-dependent manner. Expression of the RhoA inhibitor C3-transferase blocked the internalization of complement-opsonized promastigotes, whereas the dominant-negative Rac1N17 blocked the uptake of unopsonized promastigotes. The dominant-negative Cdc42N17 inhibited LPG-mediated phagosomal accumulation of F-actin and retention of Arp2/3 and Myosin. Thus, our data suggest that the effect of LPG on the accumulation of periphagosomal F-actin is the consequence of an abnormal retention or activation of Cdc42 at the phagosome.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 it