Mesenchymal stem cells induce dynamic immunomodulation of airway and systemic immune cells in vivo but do not improve survival for mice with H1N1 virus-induced acute lung injury
Notice bibliographique
Résumé
Introduction: Influenza A virus (IAV)-induced acute lung injury (ALI) is characterized by pronounced proinflammatory activation and respiratory lung dysfunction. In this study, we performed deep immune profiling on airway and circulating immune cells to examine the effect of immunomodulation and therapeutic outcomes of mesenchymal stem cells (MSCs) therapy in mice with IAV-induced ALI. Methods: Animals were inoculated intranasally with H1N1 IAV, followed by intravenous administration of vehicle, or human clinical-grade, bone marrow-derived MSCs 24-h later, and monitored for six days to evaluate the survival. In another set of animals, bronchoalveolar lavage (BAL) fluid and whole blood were collected three days after infection for flow or mass cytometry (CyTOF) immune profiling analysis. Results: Immune cell population and phenotypic shifts in blood were mapped by CyTOF. Increases were observed in granulocytes and myeloid-derived cells in blood from vehicle-treated animals. While MSC treatment accentuated changes in these populations, naïve B, antibody-secreting B cells, and T cells were decreased in MSC-treated animals at day 3. Compared to sham animals, IAV infection induced a significant 5.5-fold increase in BAL total cell counts, including CD4 + and CD8 + T cells, CD19 + B cells, CD11b + Ly6G + neutrophils, and CD11b + Ly6C + monocytes. MSC treatment significantly decreased BAL total cell counts in IAV-infected mice, specifically the number of infiltrating CD4 + T cells and CD11b + Ly6G + neutrophils. In contrast, there were increases in CD8 + T cells, B cells, and monocytes in the alveolar space in MSC-treated animals. Phenotypic immune cell profiling of blood and BAL revealed a significantly higher proportion of the monocyte population with the M2 phenotype (CD206) in MSC-treated animals; however, this failed to confer protective effects in the survival of infected mice or reduce viral titer in the lung. Further investigation revealed that MSCs were susceptible to IAV infection, leading to increased cell death and potentially affecting their efficacy. Conclusion: These findings provided in vivo evidence that MSCs promote the selective recruitment of immune cells to the site of infection during IAV infection, with reductions in proinflammatory phenotypes. However, MSCs offered no survival benefit in IAV-infected animals, possibly due to MSCs’ H1N1 IAV susceptibility and subsequent cell death.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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 | 0,001 | 0,001 |
| 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 ».