A87 MACROPHAGE-ACTIVATED INFLAMMASOME MEDIATES RECOVERY OF INTESTINAL EPITHELIAL CELLS DURING INFECTION
Bibliographic record
Abstract
Nod-like receptor protein-3 (NLRP3) inflammasomes have been linked to various inflammatory conditions such as inflammatory bowel diseases (IBD). Conditions associated with the inflammasomes are typically characterized by an overabundance of interleukin (IL)-1β with the exception of IBD, where its dysregulation results in hypoproduction. The mouse pathogen Citrobacter rodentium, which causes IBD-like colitis, is used to understand the dynamic relationship between pathogens, the inflammasome and the epithelial barrier. We have recently shown that ATP-activated macrophages increase clearance of C. rodentium in vitro. Our hypothesis is that inflammasome activation will increase macrophage recruitment and facilitate protection of the epithelial barrier. The aim was to determine the role the inflammasome plays during macrophage-epithelial interaction during C. rodentium infection Mouse colonic epithelial cells (CMT-93) were seeded on the bottom of collagen coated transwells until tight junctions were formed using transepithelial electrical resistance (TEER). The CMT-93 cells were infected with C. rodentium on the apical membrane. ATP and LPS were used to activate the inflammasome in macrophages with YVAD as an inhibitor and added to the basolateral membrane, with tight junction permeability measured using TEER. Immunofluorescence was done using confocal microscopy looking at tight junction proteins ZO-1, occluding and claudin 1. Adherence of C. rodentium to the epithelial barrier was assessed using serial dilutions and plating on LB agar at 37°C overnight. ATP-activated macrophages were increased at the apical membrane during C. rodentium infection of epithelial cells. Tight junction proteins Claudin-1, Occludin, and ZO-1 were found on macrophages using immunofluorescence. The presence of epithelial ZO-1 rings were observed during C. rodenitum infection through immunofluorescence. C. rodentium adherence was found to be significantly reduced, together with an increase in epithelial TEER recovery; this was inhibited using YVAD. These data suggest that the inflammasome is an important mediator for pathogen clearance by macrophages. Some individuals with Crohn Disease that have a decreased ability to produce IL-1β may be more susceptible to infection, as they cannot clear a pathogen. Furthermore, the role of the epithelial cell in this relationship is critical to understanding why the epithelial barrier in IBD patients is disrupted. CCCCCA
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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) | 0.001 | 0.001 |
| 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) | 0.003 | 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".