Academic Journal
Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life
| العنوان: | Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life |
|---|---|
| المؤلفون: | Belnoue, Elodie, Fontannaz, Paola, Rochat, Anne-Françoise, Tougne, Chantal, Bergthaler, Andréas, Lambert, Paul Henri, Pinschewer, Daniel, Siegrist, Claire-Anne |
| المصدر: | ISSN: 1932-6203 ; PloS one, vol. 8, no. 12 (2013) e85302. |
| سنة النشر: | 2013 |
| المجموعة: | Université de Genève: Archive ouverte UNIGE |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/616.07, info:eu-repo/classification/ddc/618 |
| الوصف: | INFANT MORTALITY FROM VIRAL INFECTION REMAINS A MAJOR GLOBAL HEALTH CONCERN: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8(+) T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC), which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8) is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/24376875; https://archive-ouverte.unige.ch/unige:35596; unige:35596 |
| الاتاحة: | https://archive-ouverte.unige.ch/unige:35596 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E6F91C22 |
| قاعدة البيانات: | BASE |
كن أول من يترك تعليقا!