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Pré-Publication, Document De Travail Année : 2020

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

Sonia Ghilas
  • Fonction : Auteur
Marc Ambrosini
  • Fonction : Auteur
Jean-Charles Cancel
  • Fonction : Auteur
Marion Massé
Hugues Lelouard
Marc Dalod
Karine Crozat

Résumé

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.

Domaines

Immunologie
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Dates et versions

hal-03007515 , version 1 (16-11-2020)

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Sonia Ghilas, Marc Ambrosini, Jean-Charles Cancel, Marion Massé, Hugues Lelouard, et al.. NK cells orchestrate splenic cDC1 migration to potentiate antiviral protective CD8+ T cell responses. 2020. ⟨hal-03007515⟩

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CNRS UNIV-AMU
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