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NK cells orchestrate splenic cDC1 migration to potentiate antiviral protective CD8+ T cell responses

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Ghilas, Sonia | Ambrosini, Marc | Cancel, Jean-Charles | Massé, Marion | Lelouard, Hugues | Dalod, Marc | Crozat, Karine

Edité par CCSD -

A successful immune response relies on a tightly regulated delivery of the right signals to the right cells at the right time. Here we show that innate and innate-like lymphocytes use two mechanisms to orchestrate in time and space the functions of conventional type 1 dendritic cells (cDC1) in spleen. Early after murine cytomegalovirus infection, XCL1 production by lymphocytes with innate functions attracts red pulp cDC1 near IFN-γ-producing NK cells, generating superclusters around infected cells in the marginal zone. There, cDC1 and NK cells physically interact reinforcing their reciprocal activation. Targeted IL-12 delivery and IL-15/IL-15Rα transpresentation by cDC1 trigger NK cell activation and expansion. In return, activated NK cells deliver GM-CSF to cDC1, triggering their CCR7-dependent relocalization into the T cell zone. This NK cell-dependent licensing of cDC1 accelerates the priming of virus-specific CD8 + T cells. Our findings reveal a novel mechanism through which cDC1 bridge innate and adaptive immunity.

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