Benefits of Antibiotics During Viral Infections: Immuno‐Modulating Properties of Tulathromycin in Porcine Reproductive and Respiratory Syndrome
Notice bibliographique
Résumé
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive‐strand RNA virus that grows in primary alveolar macrophages and causes acute pneumonia in pigs. PRRSV is a major concern in the swine industry with a total cost of productivity losses estimated at $600 million annually in the U.S. alone. However, due to its high antigenic variability, and poorly understood immunopathogenesis, there is currently no treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections, including Actinobacillus pleuropneumoniae , begs the question of the value of antibiotics for the treatment of the disease it causes. Tulathromycin, a macrolide used for the treatment and prevention of respiratory disease in pigs and cattle, has been shown to exhibit potent immuno‐modulating properties [1]. We hypothesize that tulathromycin attenuates the detrimental effects of PRRSV in porcine macrophages. This may help characterize novel mechanism through which an anti‐microbial agent may deliver clinical benefits in the context of a viral infection. Aims 1) Determine if Tulathromycin has direct anti‐viral effects in PRRSV‐infected porcine macrophages. 2) Identify new immuno‐modulating effects of Tulathromycin in PRRSV‐infected macrophages. Methods Porcine monocytes were isolated from peripheral blood of healthy piglets. Seven days‐old monocyte‐derived macrophages were treated with Tulathromycin (1 mg/ml) or untreated (control) and incubated for 1h at 37°C. Macrophages were then cultured in media alone, or with PRRSV (MOI of 1) for 2h to 24h. (1) Extracellular and intracellular Viral titers were measured at 2h, 24h, and 48h post‐infection. (2) Macrophage activation was monitored by morphological changes and confirmed with IL‐8 ELISA and ROS production assays at 2h, 6h, 12h or 24h. (3) Phagocytosis properties were assessed by measuring zymosan particles (1 μg/mL) or 3μM opsonized latex beads (ratio beads: cells, 10:1) engulfment assay (4) Cell death ELISA, Annexin V immunostaining and lactate dehydrogenase assay were performed to evaluate the effects of Tulathromycin on PRRSV‐induced necrosis and apoptosis. Results (1) Tulathromycin did not change PRRSV particle forming unit (pfu) in macrophages at any time of infection (2.1×10 4 PFU/mL with tulathromycin versus 1.9×10 4 PFU/mL for control) (2). Exposure to PRRSV increased macrophage‐induced production of IL‐8 and ROS by more than four times compared to control. Pre‐treatment with tulathromycin significantly attenuated PRRSV‐induced macrophage activation (i.e. 1.85 times compared to untreated macrophages). (3) Macrophage phagocytosis of both zymosan and latex beads was impaired by PRRSV. Tulathromycin was able to restore phagocytic functions in PRRSV‐infected macrophages to control values. (4) Finally, Tulathromycin reduced viral induced necrosis but synergized with the virus to induce apoptosis. Conclusion Our results demonstrate that Tulathromycin attenuates macrophage‐driven inflammatory response induced by PRRSV, restores PRRSV‐induced phagocytic impairment, and inhibits cell necrosis. These effects occur in the absence of a direct anti‐viral activity. Together, these data demonstrate the potential clinical benefits of Tulathromycin in the context of PRRSV‐induced pneumonia through the modulation of a viral‐induced macrophage‐driven inflammation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0,000 | 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) | 0,001 | 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 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 ».