Modulation of the host innate immune response by «Leishmania» parasites
Bibliographic record
Abstract
Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses in order to survive inside the mammalian host. Among these mechanisms are the rapid activation of phosphatases that in turn will inactivate protein kinases and transcription factors, causing abrogation of nitric oxide (NO) production and induction of immunosuppressive molecules. This doctoral thesis discusses novel mechanisms of how the parasite modulates the immune response of macrophages and dendritic cells. Herein, we describe the role of Myeloid Related Proteins (MRPs) 8 and 14 during Leishmania infection. MRPs 8/14 are produced by neutrophils and are able to induce microbicidal activity in macrophages. We present data that shows that priming macrophages with MRP 8/14 before infection induces their activation. However, infection with L. major prior to MRP stimulation significantly decreases their activation. In vivo studies showed that abrogation of MRPs resulted in an increased parasitic burden, whereas injection of recombinant MRPs (rMRPs) reduced the size of the lesion and the parasitic load. One of the main mechanisms that Leishmania parasites utilize to subvert the innate immune response is the alteration of transcription factors (TFs). In this thesis, we have shown that upon Leishmania infection, AP-1 activity is abolished and this correlates with the nuclear degradation of AP-1 subunits. Of interest, c-Jun, the main AP-1 activator is degraded and cleaved by Leishmania inside the nucleus in a GP63 dependent manner. Despite the fact that macrophages have been considered as preferred hosts for Leishmania parasites, other cells have been described as possible hosts. Finally, we discuss the effect of Leishmania infection in dendritic cells (DCs) and how this pathogen affects their maturation and capacity to present antigen. In addition, we found that Leishmania is able to activate phosphatases to inactivate signalling pathways in these cells. Collectively, o
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How this classification was reachedexpand
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".