Human Mucin-2–Producing Colonic Goblet-Like Cells Secrete the Chemokine CXCL8 by Activating Multiple Proinflammatory Pathways in Response to Entamoeba histolytica
Bibliographic record
Abstract
The mucus layer produced by highly stressed goblet cells forms a protective shield in the gut to protect the underlying mucosal epithelial cells from external threats. Hypersecretion and depletion of mucin-2 (MUC2) mucin from goblet cells is characteristic of symptomatic Entamoeba histolytica infections. It was hypothesized that MUC2 depleted goblet cells could mount a second line of innate host defense by producing proinflammatory cytokines. To investigate this, whether E. histolytica could stimulate proinflammatory responses in wild-type (WT) high MUC2 mucin-producing goblet-like cells and in clustered regularly interspaced palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) gene-edited MUC2KO cells was investigated. In response to live E. histolytica and soluble E. histolytica proteins, WT, and to a lesser extent, MUC2KO cells produced high levels of CXCL8. Entamoeba histolytica temporally induced greater levels of CXCL8 mRNA expression and protein secretion in WT versus MUC2KO cells, which was abrogated with alleviation of endoplasmic reticulum stress with the NADPH-oxidase inhibitor diphenyleneiodonium chloride. WT cells produced elevated reactive oxygen species that induced longer half-lives of CXCL8 transcripts, which was abrogated with diphenyleneiodonium chloride. Western blot and proteomic analyses revealed that WT cells, but not MUC2KO cells, were basally primed to respond to external stressors and responded to E. histolytica through rapid activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase, mitogen-activated protein kinase/p38, and phosphatidylinositol 3-kinase/Akt pathways, to induce CXCL8. These results suggest that colonic goblet-like cells defend against E. histolytica infections by hypersecreting mucus and produce the chemokine, CXCL8, to recruit neutrophils.
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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".