A14 INFLAMMASOME ACTIVATION COORDINATES INTESTINAL MUCOSAL DEFENSE AGAINST THE ENTERIC BACTERIAL PATHOGEN SALMONELLA ENTERICASEROVAR TYPHIMURIUM.
Bibliographic record
Abstract
Intestinal epithelial cells (IECs) play a central role in the coordination of intestinal homeostasis. They must strike a careful balance to temper pro-inflammatory responses against the intestinal microbiota, while remaining vigilant and rapidly responsive when exposed to a noxious stimulus such as an enteric pathogen. One early response mechanism by which IECs engage in immune defense is through the activation of an IEC-specific inflammasome. This activation triggers the extrusion of infected IEC into the gut lumen, ultimately restricting Salmonella enterica serovar Typhimurium from escaping the gut and spreading systemically. However, it appears the role of the inflammasome in gut defense is not just restricted to IEC shedding but it also plays a key role in mucin secretion and antimicrobial lectin production. Here, we investigate the role of the inflammasome in mucosal defense against S. Typhimurium SL1344. This study employed a streptomycin pretreatment S. Typhimurium mouse infection model as well as various cell and immunofluorescent staining to characterize the role of the intestinal inflammasome. Streptomycin-pretreated C57BL/6, Casp1/11 deficient (−/−) and Casp11−/− mice were orally infected and S. Typhimurium loads determined for each respective tissue at 18h and 72h post infection. Increased pathogen burdens were observed for both caspase-deficient mice compared to wild type, with increased systemic spread seen in the mesenteric lymph nodes, liver and spleen at both time points for Casp1/11−/− mice but only at 72h for Casp11 −/−. Interestingly, at 18h, despite increased bacterial loads, cecal pathology scores were decreased in both Casp1/11−/− and Casp11−/− mice, as compared to wild type. This was accompanied by increased intracellular S. Typhimurium immunofluorescence staining. Also, cecal mucin layer thickness, as measured by Alcian Blue as well as MUC2 immunofluorescence staining were similar amongst all mouse strains before infection, but were decreased in both Casp1/11−/− and Casp11−/− mice as compared to wild type after infection. Finally, expression of the antimicrobial lectins REG3γ and REG3β were significantly decreased in Casp11−/− mice as compared to wild type mice and minimal staining for REG3β was observed in both caspase deficient mice. These results indicate that the gut epithelium utilizes inflammasome signaling to coordinate multiple layers of innate defense at the gut mucosal surface to ultimately restrict enteric pathogen infections and systemic spread. CCC, CIHRNSERC, UBC
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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) | 0.001 | 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 | 0.001 | 0.001 |
| 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".