期刊
JOURNAL OF IMMUNOLOGY
卷 193, 期 3, 页码 1151-1161出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301440
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资金
- Ligue Nationale Contre le Cancer (Equipe Labellisee)
- Institut National du Cancer/Canceropole Ile de France
- Banque Privee Europeenne
- European Union (Advanced Immunization Technologies) [280873]
- Fondo de Investigacion Sanitaria [PI11/02327]
- Union Temporal de Empresas project Centro de Investigacion Medica Aplicada
- Asociacion Espanola Contra el Cancer
- Ministerio de Educacion y Ciencia [RYC-2007-00928]
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-beta 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-beta 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.
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