1532. Increased Risk of Bacterial, Fungal and Other Viral Infections During CMV Infection: Decreased Cytokine Production in Response to Toll-Like Receptor Ligands
Notice bibliographique
Résumé
In the solid-organ transplant (SOT) setting, CMV is an immunomodulatory virus that indirectly increases the risk for bacterial, fungal and viral infections. However, the pathogenesis of this phenomenon is poorly understood. The aim of our study was to determine whether inflammatory responses to different Toll-like receptor ligands are blunted during CMV infection in SOT patients. CMV D+/R− SOT patients had blood drawn at the end of CMV prophylaxis and then weekly after onset of CMV viremia. PBMCs were extracted and incubated for 24 hours in the presence of bacterial (LPS), fungal (Zymosan [ZYM]), and viral (Resiquimod [R848]) ligands. Proinflammatory (IL1β), Th1 (IFNγ), Th2 (IL4), immunoregulatory (IL10), and chemotactic (MCP1) cytokines were measured in the supernatant by multiplex ELISA. Thirty-eight SOT patients were followed for at least 9 months. Patients who developed subsequent CMV infection had lower cytokines in response to bacterial, fungal and viral ligands (LPS, ZYM, and R848) at the end of prophylaxis compared with those with no CMV infection. These results were independent of immunosuppression and peripheral blood cell counts. Specifically, these trends were significantly different with respect to IFNγ, IL1β, and IL10 production in response to LPS (P = 0.003, 0.003, and 0.039, respectively), R848 (P < 0.001, 0.039, and <0.001, respectively) and ZYM (P = 0.039, 0.003, and 0.003, respectively), as well as for MCP1 in response to R848 or ZYM (P = 0.039 for both). In the cohort with CMV infection, cytokine responses to TLR ligands were even lower during the acute CMV infection when compared with the end of prophylaxis, although this was significant only for IL10 production after R848 stimulation (P = 0.034). There was no influence of CMV viral load or duration of viremia on cytokine levels. Response to non-CMV antigens during CMV infection was blunted supporting the clinical observation in transplant recipients that CMV infection increases susceptibility to bacterial, fungal, and other viral infections. However, inherent differences in patients that are neither directly related to CMV nor to their net level of immunosuppression also contribute to this increased susceptibility, as cytokine levels at the end of prophylaxis were lower among patients with compared with those without subsequent CMV infection. All authors: No reported disclosures.
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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 | 0,002 |
| 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 | 0,001 | 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) | 0,001 | 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 ».