期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 122, 期 5, 页码 1628-1643出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI60660
关键词
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资金
- Cellomics and Comparative Medicine Units
- Department of Vascular Biology and Inflammation at the CNIC
- CNIC
- Spanish Ministry of Science and Innovation [SAF-2010-15120, RYC-2009-04235]
- European Research Council (ERC) [ERC-2010-StG 260414]
- Cancer Research UK [15689] Funding Source: researchfish
In order to prime T cells, DCs integrate signals emanating directly from pathogens and from their noxious action on the host. DNGR-1 (CLEC9A) is a DC-restricted receptor that detects dead cells. Therefore, we investigated the possibility that DNGR-1 affects immunity to cytopathic viruses. DNGR-1 was essential for cross-presentation of dying vaccinia virus-infected (VACV-infected) cells to CD8(+) T cells in vitro. Following injection of VACV or VACV-infected cells into mice, DNGR-1 detected the ligancl in dying infected cells and mediated cross-priming of anti-VACV CD8(+) T cells. Loss of DNGR-1 impaired the CD8(+) cytotoxic response to VACV, especially against those virus strains that are most dependent on cross-presentation. The decrease in total anti-VACV CTL activity was associated with a profound increase in viral load and delayed resolution of the primary lesion. In addition, lack of DNGR-1 markedly diminished protection from infection induced by vaccination with the modified vaccinia Ankara (MVA) strain. DNGR-1 thus contributes to anti-VACV immunity, following both primary infection and vaccination. The non-redundant ability of DNGR-1 to regulate cross-presentation of viral antigens suggests that this form of regulation of antiviral immunity could be exploited for vaccination.
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