SHP-1/PTP-1B Macrophage interactome upon «Leishmania mexicana» infection
Bibliographic record
Abstract
Leishmaniasis is a disease endemic to 88 countries that affects 12 million people worldwide. The causative agents are species of the genus Leishmania, with the clinical manifestation of this disease depending on the species. Once in the host, the parasite lives inside various cell types including macrophages, and must modulate the host cell functions to survive. Host macrophages are capable of detecting various foreign molecules and mounting cellular responses. Macrophages engulf their target pathogen and, through the maturation of the phagolysosome, will destroy it. To prevent aberrant activation of the cell, macrophages use protein tyrosine phosphatases (PTPs) to return activation signals (i.e. phosphorylation) in signalling pathways to their resting state. Leishmania employs multiple strategies to alter the host signalling and functions. One such mechanism is the ability of the parasite to activate host PTPs by proteolytic cleavage. In this study, we isolated the plasma membrane and the cytoplasm of macrophages to identify the localization of and alteration in host PTPs, PTP-1B and SHP-1 during infection with Leishmania mexicana. We observed that during an infection, cleaved SHP-1 is no longer found at the plasma membrane. Prior to an infection, we also noted that the proportion of PTP-1B and SHP-1 located in the plasma membrane is minute compared to the amount found in the cytoplasm. The second part of the study was to compare the interactomes of PTP-1B and SHP-1 in resting cells and during an infection. We noticed distinct groups of proteins interacted with these PTPs, including proteins involved in translation and RNA manipulation, cell metabolism, and subcellular localization. We also observed large variations in the level of interaction with the interactants and the PTPs. This study demonstrates Leishmania refined ability to control the host cell to prevent its destruction.
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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".