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

Authors:
Sonia Assil
Sonia Assil
Université de Lyon
France
Elodie Decembre
Elodie Decembre
Université Claude Bernard Lyon 1
Lee Sherry
Lee Sherry
University of St Andrews
United Kingdom
Omran Allatif
Omran Allatif
Centre International de Recherche en Infectiologie (CIRI)
Lyon | France
Brian Webster
Brian Webster
Weill Medical College of Cornell University
United States
Marlene Dreux
Marlene Dreux
United States

Cell Host Microbe 2019 05 16;25(5):730-745.e6. Epub 2019 Apr 16.

CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, Lyon F-69007, France. Electronic address:

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 αβ 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.

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http://dx.doi.org/10.1016/j.chom.2019.03.005DOI Listing
May 2019
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