en
Scientific article
Open access
English

Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life

Published inPloS one, vol. 8, no. 12, e85302
Publication date2013
Abstract

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.

Citation (ISO format)
BELNOUE, Elodie et al. Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life. In: PloS one, 2013, vol. 8, n° 12, p. e85302. doi: 10.1371/journal.pone.0085302
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
625views
353downloads

Technical informations

Creation02/27/2014 1:30:00 PM
First validation02/27/2014 1:30:00 PM
Update time03/14/2023 9:07:04 PM
Status update03/14/2023 9:07:04 PM
Last indexation02/12/2024 11:18:55 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack