Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts

Nat Commun. 2018 Jul 9;9(1):2658. doi: 10.1038/s41467-018-05077-9.

Abstract

Interaction of T cell with antigen-bearing dendritic cells (DC) results in T cell activation, but whether this interaction has physiological consequences on DC function is largely unexplored. Here we show that when antigen-bearing DCs contact T cells, DCs initiate anti-pathogenic programs. Signals of this interaction are transmitted from the T cell to the DC, through extracellular vesicles (EV) that contain genomic and mitochondrial DNA, to induce antiviral responses via the cGAS/STING cytosolic DNA-sensing pathway and expression of IRF3-dependent interferon regulated genes. Moreover, EV-treated DCs are more resistant to subsequent viral infections. In summary, our results show that T cells prime DCs through the transfer of exosomal DNA, supporting a specific role for antigen-dependent contacts in conferring protection to DCs against pathogen infection. The reciprocal communication between innate and adaptive immune cells thus allow efficacious responses to unknown threats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • Antigens / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / immunology*
  • Extracellular Vesicles / metabolism
  • Gene Expression / immunology
  • HEK293 Cells
  • Humans
  • Interferons / immunology
  • Interferons / metabolism
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Viruses / immunology

Substances

  • Antigens
  • Interferons