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J Immunol. 2014 Aug 1;193(3):1151-61. doi: 10.4049/jimmunol.1301440. Epub 2014 Jun 27.

Conventional but not plasmacytoid dendritic cells foster the systemic virus-induced type I IFN response needed for efficient CD8 T cell priming.

Author information

1
Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain; mshervas@unav.es claude.leclerc@pasteur.fr.
2
Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain;
3
Inmunología y Genética Aplicada, S.A., Madrid 28037, Spain;
4
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8147, Université René Descartes Paris V, Hôpital Necker, Paris F-75015, France;
5
Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris F-75015, France; and INSERM, Unité 1041, Paris F-75015, France mshervas@unav.es claude.leclerc@pasteur.fr.

Abstract

Plasmacytoid dendritic cells (pDCs) are considered to be the principal type-I IFN (IFN-I) source in response to viruses, whereas the contribution of conventional DCs (cDCs) has been underestimated because, on a per-cell basis, they are not considered professional IFN-I-producing cells. We have investigated their respective roles in the IFN-I response required for CTL activation. Using a nonreplicative virus, baculovirus, we show that despite the high IFN-I-producing abilities of pDCs, in vivo cDCs but not pDCs are the pivotal IFN-I producers upon viral injection, as demonstrated by selective pDC or cDC depletion. The pathway involved in the virus-triggered IFN-I response is dependent on TLR9/MyD88 in pDCs and on stimulator of IFN genes (STING) in cDCs. Importantly, STING is the key molecule for the systemic baculovirus-induced IFN-I response required for CTL priming. The supremacy of cDCs over pDCs in fostering the IFN-I response required for CTL activation was also verified in the lymphocytic choriomeningitis virus model, in which IFN-β promoter stimulator 1 plays the role of STING. However, when the TLR-independent virus-triggered IFN-I production is impaired, the pDC-induced IFNs-I have a primary impact on CTL activation, as shown by the detrimental effect of pDC depletion and IFN-I signaling blockade on the residual lymphocytic choriomeningitis virus-triggered CTL response detected in IFN-β promoter stimulator 1(-/-) mice. Our findings reveal that cDCs play a major role in the TLR-independent virus-triggered IFN-I production required for CTL priming, whereas pDC-induced IFNs-I are dispensable but become relevant when the TLR-independent IFN-I response is impaired.

PMID:
24973449
PMCID:
PMC4105236
DOI:
10.4049/jimmunol.1301440
[Indexed for MEDLINE]
Free PMC Article

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