Asthma, childhood exposures and genetics shape anti-viral cytokine responses in humans
Notice bibliographique
Résumé
Respiratory virus infections are associated with asthma pathogenesis and exacerbations in children and adults. Unfortunately, it remains largely unknown whether innate and adaptive T cell anti-viral immunity differs in allergic disease versus health. Here, we established a short-term primary cell culture system using human peripheral blood mononuclear cells (PBMC) optimized for measuring immune responses to reovirus, respiratory syncytial virus (RSV) and metapneumovirus (MPV) based on virus-specific cytokine and chemokine production. The prevalence and intensity of innate and adaptive responses in children and adult populations was addressed. Using this in vitro model of human anti-viral immunity, we tested our global hypothesis that asthmatics mount anti-viral cytokine responses to respiratory viruses that differ from those of healthy individuals. MPV and RSV, although both ubiquitous and leading to very high levels of infection, seroconversion and clinically similar presentation in the population, evoke distinct innate and adaptive T cell-dependent cytokine responses. Reovirus induced exceptionally strong IFN recall responses concomitant with intense IL-10 production, which were independent of viral replication in PBMC. Surprisingly, despite Type 1 cytokine production dominated adaptive immune responses in both asthmatic and non-asthmatic individuals, asthmatics exhibited significantly stronger pro-inflammatory IFNγ and IL-10 production towards virus stimulation than non-asthmatic children and adults. Moreover, children with current AHR, regardless of asthmatic status, exhibit a greater frequency and intensity of IFNγ responses towards pneumoviruses than do non-AHR counterparts. Conversely, expression of chemokine CCL5 was substantially weaker in asthmatics, and was further decreased in children with AHR and familial history of asthma. This pattern of enhanced pro-inflammatory and deficient anti-viral CCL5 responses towards pneumoviruses in children with markers of symptomatic asthma or AHR may underlie the enhanced sensitivity of these children to experience breathing difficulties following infection with respiratory viruses. Furthermore, we have clearly demonstrated a gene by environment interaction, whereby ETS exposure in children with familial asthma results in suppressed anti-viral IFNγ and IL-10 production. Therefore, we have attempted to determine whether genetic variation affects the intermediate phenotype of anti-viral immunity, in the population and dependent on clinical status. In summary, we have demonstrated that asthma, childhood exposures and genetics shape anti-viral cytokine responses in human. These findings have a substantial impact for physicians deciding the contextually appropriate treatment for asthma symptoms in their patients and could have implications for experimentation relating to mechanisms of disease, clinical practice and development of appropriate therapeutics.
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 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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,001 | 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 ».