Mast Cells-derived Exosomes Promote the Development of Experimental Cerebral Malaria
Bibliographic record
Abstract
Abstract Background: Cerebral malaria (CM) is a severe neurological manifestation caused by Plasmodium infection, with high morbidity and mortality rate, and long-term cognitive impairments in survivors. Exosomes are cell-derived nano-vesicles secreted by virtually all types of cells and serve as mediators of intercellular communication. Studies have demonstrated that mast cells (MCs) play a critical role in mediating malaria severity, however, the potential functions and pathological mechanisms of MCs-derived exosome (MCs-Exo) impacting on CM pathogenesis remain largely unknown. Methods: Herein, we utilized an experimental CM (ECM) murine model (C57BL/6 mice infected with P. berghei ANKA), and then intravenously (i.v.) injected MCs-Exo into ECM mice to investigate the effect of MCs-Exo on ECM pathogenies. We also used an in vitro model by investigating the pathogenesis development of brain microvascular endothelial cells line (bEnd.3 cells) upon MCs-Exo treatment after P. berghei ANKA blood-stage soluble antigen (PbAg) stimulation. Results: MCs-Exo were successfully isolated from culture supernatants of mouse MCs line (P815 cells) stimulated with PbAg, characterized by spherical vesicles with the diameter of 30–150 nm, expressing of typical exosomal markers, including CD9, CD81, and CD63. In vivo and ex vivo tracking showed that DiR-labeled MCs-Exo were taken up by liver and brain tissues after 6 h of i.v. injection. Compared with naive mice, ECM mice exhibited higher numbers of MCs and higher levels of MCs degranulation in various tissues (e.g., brain, cervical lymph node, and skin). The present of MCs-Exo dramatically shortened survival time, elevated incident of ECM, exacerbated liver and brain histopathological damage, promoted Th1 cytokine response, and aggravated brain vascular endothelial activation and blood brain barrier breakdown in ECM mice. Interestingly, compared with bEnd.3 cells stimulated with PbAg, the treatment of MCs-Exo led to decrease of cells viability, increase the mRNA levels of Ang-2, CCL2, CXCL1, and CXCL9, and decrease the mRNA levels of Ang-1, ZO-1, and Claudin-5. Conclusions: Thus, our data suggest that MCs-Exo could promote pathogenesis of ECM in mice.
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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) | 0.001 | 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) | 0.002 | 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".