<i>Entamoeba histolytica</i> Stimulates the Release of the Alarmin Molecule HMGB1 upon Contact with Macrophages
Bibliographic record
Abstract
Entamoeba histolytica ( Eh ) is the causative agent of amebiasis, which occurs in 10% of infected individuals when the parasite invades the underlying colonic mucosa. Parasite‐induced host pro‐inflammatory responses are critical in disease pathogenesis, but the mechanisms underlying this response is poorly illustrated. The contact between Eh and macrophages triggers a raging pro‐inflammatory response by activating NLRP3 inflammasome (IL‐1β) and other uncharacterized pathways (TNF‐α). High Mobility Group Box 1 protein (HMGB1) is a critical mediator of inflammation during infection and it shapes the magnitude and degree of the inflammatory response. HMGB1 is a non‐histone nuclear protein, which have overlapping binding side with histone H1 in the chromatin. It is released in the extracellular space during infection by activated or damaged immune cells and act as an alarmin molecule. In this study, we investigated the early release of HMGB1 upon Eh infection with macrophages and identification of the parasite virulent factors that initiated this response. Human monocytic cell line (THP‐1) and mouse bone marrow derived macrophages (BMDMs) were treated with live Eh , Eh components for different time point and western blotting was used to quantify HMGB1 secretion. Only stimulation with live Eh but not Eh components triggered robust time‐dependent (as early as 5 minutes) secretion of HMGB1. HMGB1 release from macrophage was contact‐dependent as inhibiting the Gallectin adhesion with exogenous galactose abrogated HMGB1 secretion. Another Eh surface virulent factor cysteine protease 5 ( Eh CP5) partially inhibited HMGB1 release, and the enzymatic activity of the CP5 was not required for the secretion. Moreover, HMGB1 protein secretion was independent of caspase‐1 activation, as secretion was not inhibited with the Pan caspase inhibitor, Z‐VAD‐fmk. Similar results were obtained using BMDMs from caspase‐1 − / − mice treated with live Eh . Surprisingly, there was the simultaneous release of the nuclear protein histone H1 along with the HMGB1 upon Eh infection. These results demonstrate that the potent pro‐inflammatory mediator HMGB1 release is the earliest innate response upon Eh contact with macrophages. This mediator can act by itself or along with other molecules as a danger signal (alarmin response) to sense invasive infection that can attract bystander cells and/or promote extensive inflammation, which is critical in disease pathogenesis. Support or Funding Information 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 | 0.000 |
| 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".