A52 ANALYSIS AND CHARACTERIZATION OF THE EXCRETED/SECRETED PRODUCTS OF PARASITIC HELMINTHS AS IMMUNOMODULATORS OF INFLAMMATORY BOWEL DISEASE (IBD)
Notice bibliographique
Résumé
Abstract Background Parasitic helminths Trichuris suis and Ascaris suum are known to modulate host immune responses. This is thought to be mediated by the secretome, or excreted factors released by these parasites. We are interested in the excretory/secretory products (ESP, TsESP and AsESP) and mechanisms responsible for modulating immune disfunciton in autoinflammatory diseases. Aims This research studies the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to describe the cellular response in vitro, as well as the systemic response in vivo, to better characterize the scope of immune modulation in ESP treatment. Methods ESPs were collected from T. suis or A. suum-conditioned media and proteins and metabolites were isolated. Bone marrow (BM) derived macrophages (BMDM) from C57BL6 mice, were treated with ESP fractions, stimulated with LPS, and secreted cytokines levels measured. Alternatively, undifferentiated BM was incubated with or without metabolites throughout the process of differentiation. Using a DSS-colitis model, mice were given 3% DSS or water, then treated with ESP or PBS once daily by IP injection. Colon lengths and TNFα mRNA levels were measured and histological preparations were scored to assess pathology. ESP with bioactivity were selected for further HPLC analysis. Fractions were collected and assayed for bioactivity. Results BMDM treated with T. suis or A. suum crude ESP decreased secretion of TNFα and increased IL-10. BMDM precursors incubated with A. suum metabolites during differentiation had fewer BMDM-like cells. Cytokine analysis showed decreased TNFα secretion. Experiments with Alamar suggested that metabolites remmodelled the BMDM metabolic pathways. These effects are being explored further. We found that metabolites released by A. suum improved DSS-colitis. Specifically, mice with DSS-induced colitis given IP metabolites had reduced colon shortening compared to PBS controls, a lower histologic damage score, as well as lower levels TNFα mRNA expression in gut epithelial cells. HPLC showed multiple peaks from crudes analyzed at 210 nm and 280 nm. HPLC fractions used to treat BMDM yielded varying secretion of TNFα. Bioactive fractions from HPLC coincide with the UV/Vis peaks, further suggesting they could be isolated and studied for immunomodulation. Conclusions These data suggested that ESP contains immunomodulators that may provide lead therapeutic compounds for patients with IBD. Helminth-derived components can immunologically polarize a response in vitro, as well as alter disease recovery in DSS colitis. HPLC fractionation and biological testing suggest that a bioactive molecule can be obtained. Further analysis must be done to determine structure using mass spectrometry and NMR analysis. Funding Agencies Natural Sciences and Engineering Research Council of Canada (NSERC) and Fonds de recherche nature et technologies Québec (FRQNT)
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».