Apr 24, 2020

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

BioRxiv : the Preprint Server for Biology
S. GhilasKarine Crozat

Abstract

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-{gamma}-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-15R 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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Mentioned in this Paper

Real-Time Polymerase Chain Reaction
Size
Homogeneous Organ
Gene Expression
Cell Growth
Mouse Blood
Cell Cycle
RNA, Messenger
Approach
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