<i>Entamoeba histolytica</i> ‐Induced Caspase‐4/11 Activation Elicits a Pro‐Inflammatory Response in Macrophages
Bibliographic record
Abstract
Entamoeba histolytica ( Eh ) is a protozoan parasite that colonizes in/on the mucus layer and in 10% of individuals, Eh invades the colonic mucosa to cause amebic colitis. A hallmark of amebiasis is acute intestinal inflammation dominated by the secretion of pro‐inflammatory cytokines, interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α. Eh in contact with macrophages activates caspase‐1 by the inflammasome complex resulting in the maturation of IL‐1β and ‐18. The role of inflammatory caspase‐4, ‐5, and ‐12 in humans are less understood. Caspase‐11, the murine homolog of caspase‐4, mediates non‐canonical inflammasome activation in response to particular pathogens, suggesting that caspase‐4 may have similar roles. As caspase‐4/11 might be an immune sensor in Eh infection the aim of this study was to identify a signature role for caspase‐4/11 in Eh ‐induced macrophage responses. To determine if caspase‐4/11 was involved in inflammasome signalling, the gene was silenced with siRNA. Knockdown of caspase‐4/11 did not affect caspase‐1 activation or IL‐1β secretion in response to Eh . However, multiplex cytokine arrays showed marked up regulation of TNF‐α, MIP‐1β, and KC suggesting that caspase‐4/11 may have regulatory roles in the secretion of distinct cytokines/chemokines. Although there was no evidence for crosstalk between caspase‐4/11 and caspase‐1, these inflammatory caspases seem to play a critical role in regulating other cytokines/chemokines that shape the overall macrophage response towards Eh infection. Elucidating the role these inflammatory caspases play in Eh disease pathogenesis may shed light on new therapeutics to treat amebiasis. Grant Support: NSERC
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".