2024-03-29T11:10:45Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/97132023-10-09T14:35:08Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Iborra, Salvador
author
Izquierdo-Fernandez, Helena Maria
author
Martinez-Lopez, Maria
author
Blanco-Menendez, Noelia
author
Reis e Sousa, Caetano
author
Sancho, David
author
2012-05
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 ligand 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.
J Clin Invest. 2012; 122(5):1628-43
0021-9738
http://hdl.handle.net/20.500.12105/9713
22505455
10.1172/JCI60660
1558-8238
The Journal of clinical investigation
The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice