A116 ABERRANT IMMUNE RESPONSE AGAINST INVADING BACTERIA INCREASES MORTALITY IN MUC2 MUCIN DEFICIENT MICE IN LPS INDUCED SEPSIS
Notice bibliographique
Résumé
A physical barrier in the gut, formed mainly by the mucus bilayer, keeps gut microbiota and/or components away from translocating into host tissues. Perturbation of the mucus layer, as in inflammatory bowel diseases (IBD), leads microbial penetrants to initiate local and systemic inflammation. Unregulated inflammation can aggravate into sepsis, causing mortality due to multiple organ failure. IBD patients are at high risk for developing sepsis due to their defective gut barrier function, yet is poorly understood. Muc2-/- mice without a mucus barrier have low-grade inflammation with bacterial penetrants and is an excellent model to study chronic colitis and ideal for IBD related studies. To assess immune response in Muc2-/- mice in lipopolysaccharide (LPS) induced sepsis. LPS was administered in Muc2-/- and WT littermates intra-peritoneally (i.p.) as 5mg/kg body weight (BW) and monitored for BW loss and mortality. Mice were euthanized at 24 or 48 h. Spleen and intestinal tissue were harvested for immunophenotyping and histology. Single cell suspension of splenocytes were prepared and stained with anti CD3, CD4, CD8, CD19 and CD49b antibodies for T-cells, B-cells and NK cells. Apoptotic and dead cells were determined by Annexin V and 7-AAD staining. Immunophenotyping was done using FACS Canto and data was analyzed by FlowJo software. Bacterial penetrance into distal ileum, cecum and colonic tissue was determined using fluorescence in situ hybridization (FISH) and real time RT-PCR. Muc2-/- mice basally exhibited significantly larger numbers of splenic B-cells, CD8+ cells and NK cells than WT littermates suggesting ongoing elevated systemic inflammation. CD4+ cells were unchanged. Notably, Muc2-/- mice exhibited increased apoptosis of splenic B-cells at baseline indicating systemic inflammation and immunosuppression. Following LPS induced sepsis, we observed increased bacterial penetrance through the distal ileum, cecum and colonic walls of Muc2-/- mice at 24 and 48 h as compared to WT littermates. In WT littermates, LPS treatment led to massive accumulation and secretion of mucus (mucus plug) in the lumen that impaired bacterial translocation. Moreover, splenocytes in LPS induced sepsis showed significantly increased apoptosis of B-cells, decreased apoptosis of CD4+ and CD8+ cells in Muc2-/- as compared to WT littermates. The aberrant immune response in Muc2-/- mice was correlated with significantly increased bacterial burden in the liver and spleen resulting in rapid BW loss and mortality. Our research suggests that during chronic IBD, host immune cells may become exhausted with continual exposure to microbial penetrants leaking through the altered and/or depleted intestinal mucus barrier. This can result in aberrant immune response against invading pathogens and increased susceptibility to sepsis. CCC, CIHR
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) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,002 |
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 ».