Abnormal IFN‐γ‐dependent immunoproteasome modulation by <i>Trypanosoma cruzi</i>‐infected macrophages
Bibliographic record
Abstract
Proteasomes are the main producers of Ag loaded onto MHC class I molecules. Following IFN-gamma stimulation however, the constitutive subunits of the proteasome are replaced by the immunosubunits low molecular weight protein 2 (LMP2), multicatalytic endopeptidase complex-like 1 and low molecular weight protein 7 (LMP7), which generally heighten the immunogenecity of proteasome generated epitopes. Given that Trypanosoma cruzi, the aetiological agent of Chagas' disease, elicits a T(helper)1 response from its host if the infection is to be contained, the aim of this study was to verify whether this parasite modulates J774 and B10R mouse macrophage (MuPhi) immunoproteasome subunit and MHC class I expressions and, if so, identify the mechanism(s) responsible for that modulation. Results show that T. cruzi infection of mouse MuPhi reduces IFN-gamma-mediated immunoproteasome synthesis, along with MHC class I mRNA synthesis and cell surface expression. The infection by T. cruzi induces the release of reactive oxygen species (ROS) from MuPhi, and those ROS significantly inhibit protein tyrosine phosphatase activity, thereby leading to the activation of the SAPK/JNK signalling pathway, which is responsible for the observed IFN-gamma-mediated immunoproteasome synthesis and MHC class I down-regulation. To our knowledge, this is the first report that specifically identifies a mechanism by which a pathogen achieves immunoproteasome down-modulation.
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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".