A293 INFLAMMASOME ACTIVATION INCREASES MACROPHAGE MIGRATION THROUGH EPITHELIAL BARRIER DURING CITROBACTER RODENTIUMINFECTION
Notice bibliographique
Résumé
The proinflammatory cytokine interleukin (IL)-1β is released from macrophages and monocytes through a class of protein complexes called inflammasomes. 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 IL-1β with the exception of IBD, where its dysregulation leads to an IL-1β reduction. The mouse pathogen Citrobacter rodentium, a common mouse model pathogen for enteropathogenic E. coli, is used to understand the dynamic relationship between pathogens, the inflammasome, and the epithelial barrier. We have previously shown that ATP-activated macrophages increase clearance of C. rodentium in vitro. Our hypothesis was that inflammasome activation will increase macrophage recruitment and facilitate migration through the epithelial barrier. To determine the role of the inflammasome in bacterial-epithelial-macrophage interplay Mouse colonic epithelial cells (CMT-93) were seeded on collagen coated transwells until tight junctions were formed [documented using transepithelial electrical resistance (TEER)]. CMT-93 cells were then infected with C. rodentium on the apical membrane. ATP (2.5mM) and LPS (10ng/ml) were used to activate the inflammasome in macrophages and then added to the basolateral membrane for 24hrs. Tight junction permeability was measured every 2 hrs using TEER. Macrophage migration was observed using confocal microcopy with F4/80 as the macrophage stain along with GFP C. rodentium and epithelial ZO-1 staining. The tight junction proteins Claudin-1, Occludin, and ZO-1 were assessed in macrophages. ATP-activated macrophages were recruited to the apical membrane during C. rodentium infection of epithelial cells. C. rodentium adherence to epithelial cells after 24 hours was found to be significantly reduced and there was an increase in epithelial barrier recovery, measured by TEER; these effects were inhibited when YVAD was present. We also documented an increase in macrophage tight junction proteins during C. rodentium infection, suggesting a potential for active interaction with epithelial cells. 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, due to impairments in the ability to clear pathogens. Our multi-cell type models highlights the important relationship between epithelial cells and macrophage inflammasomes in maintaining the epithelial barrier in IBD patients, which could allow development of new treatments. CCCCCA
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».