Serum amyloid A and apolipoprotein E alter the host innate immune response elicited by malarial hemozoin (68.14)
Bibliographic record
Abstract
Abstract Malaria is one of the most important infectious diseases worldwide and still remains to be the major cause of death in tropical countries. The intraerythrocytic stage of the malaria parasite results in the production and release of hemozoin (HZ). Recently we have identified that HZ specifically interacts with serum proteins such as serum amyloid A (SAA) and apolipoprotein E (ApoE). In our current work, we were interested to determine the impact of these proteins on the macrophage’s innate immune response triggered by HZ. Since HZ induces IL-1β production via the NLRP3 inflammasome, we looked at the production of IL-1β using PMA-differentiated THP-1 cells. IL-1β, along with TNF-α, is considered to be the major contributor for malaria pathology. Our results show that SAA bound to HZ induces the production of IL-1β in a dose dependent manner. Furthermore, HZ-SAA and hemozoin-ApoE complexes phosphorylate the MAPKs specifically ERK1/2 and JNK. This is in agreement with the observation that SAA activates downstream signaling pathways via LYN resulting in the activation of ERK1/2 and JNK. Apart from IL-1β production, HZ bound serum proteins also modulate ROS production and phagocytosis in THP-1 cells. Overall, our results show that serum inflammatory proteins adhering on HZ modify its capacity to stimulate phagocytosis, IL-1β and ROS productions by THP-1 cells upon stimulation, suggesting that such cooperation could greatly influence the development of malaria-related pathologies.
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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".