THE ROLE OF THE MUCOSAL INNATE IMMUNE RESPONSE IN THE PATHOGENESIS OF ENTAMOEBA HISTOLYTICA
Bibliographic record
Abstract
Authors: Leanne Mortimer, France Moreau, Kris Chadee Faculty of Medicine, Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Gastrointestinal Research Group, University of Calgary, Alberta, Canada. E-mail: kchadee@ucalgary.ca Introduction: Entamoeba histolytica ( Eh ) is an extracellular protozoan parasite of the human colon, which occasionally breaches the intestinal barrier. Eradicating ameba that invades is essential for host survival. A defining but uncharacterized feature of amebic invasion is direct contact between ameba and host cells. This event corresponds with a massive pro-inflammatory response. To date, pathogen recognition receptors (PRR) that are activated by contact with viable Eh are unknown. Materials and Methods: We quantified inflammasome activation in macrophages using well-defined pharmacological inhibitors of the nlrp3 pathway and in macrophages that were genetically deficient for inflammasome components. Mechanistic studies investigated if the danger signal ATP could trigger the inflammasome by blocking the P 2 X 7 receptor and by enzymatic depletion of extracellular ATP. Inflammasome activation was visualized in real-time using confocal microcopy with cell-permeable caspase-1 probes. Results: Here we show that the innate immune system responds in a qualitatively different way to contact with viable Eh versus soluble ligands produced by viable or dead ameba. This unique Eh Gal-lectin contact-dependent response in macrophages was mediated by activation of the inflammasome. Soluble native Gal-lectin did not induce inflammasome activation, but was sufficient for transcriptional priming of the inflammasome and non-inflammasome-dependent pro-inflammatory cytokine release. Conclusions: Our results suggest that the inflammasome is a pathogenicity sensor for invasive Eh and identify for the first time a PRR that specifically responds to contact with intact parasites in a manner that accords with scale immune response to parasite invasion.
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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".