Plasmacytoid Dendritic Cells and Infected Cells Form an Interferogenic Synapse Required for Antiviral Responses

Abstract

Type I interferon (IFN-I) is critical for antiviral defense, and plasmacytoid dendritic cells (pDCs) are a predominant source of IFN-I during virus infection. pDC-mediated antiviral responses are stimulated upon physical contact with infected cells, during which immunostimulatory viral RNA is transferred to pDCs, leading to IFN production via the nucleic acid sensor TLR7. Using dengue, hepatitis C, and Zika viruses, we demonstrate that the contact site of pDCs with infected cells is a specialized platform we term the interferogenic synapse, which enables viral RNA transfer and antiviral responses. This synapse is formed via α L β 2 integrin-ICAM-1 adhesion complexes and the recruitment of the actin network and endocytic machinery. TLR7 signaling in pDCs promotes interferogenic synapse establishment and provides feed-forward regulation, sustaining pDC contacts with infected cells. This interferogenic synapse may allow pDCs to scan infected cells and locally secrete IFN-I, thereby confining a potentially deleterious response. Plasmacytoid dendritic cells (pDCs) sense viruses by physically contacting infected cells. Assil et al. show that the contact site between pDCs and infected cells is a specialized platform, termed an interferogenic synapse, with polarized cellular components and machinery that efficiently transfer immunostimulatory RNA to induce antiviral responses in pDCs.