Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation

PLoS Pathog. 2019 Feb 28;15(2):e1007589. doi: 10.1371/journal.ppat.1007589. eCollection 2019 Feb.

Abstract

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines
  • Dendritic Cells / physiology*
  • Galactosides / metabolism
  • Glycosylation
  • HTLV-I Infections / immunology
  • HTLV-I Infections / metabolism*
  • Human T-lymphotropic virus 1 / immunology
  • Human T-lymphotropic virus 1 / pathogenicity
  • Human T-lymphotropic virus 2 / immunology
  • Human T-lymphotropic virus 2 / pathogenicity
  • Humans
  • Immunity, Innate / physiology
  • Interferon Type I / immunology
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Jurkat Cells
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology

Substances

  • Cytokines
  • Galactosides
  • Interferon Type I
  • Interferon-alpha
  • beta-galactoside