DC‐SIGN mediated internalisation of glycosylated extracellular vesicles from Schistosoma mansoni increases activation of monocyte‐derived dendritic cells

Marije E. Kuipers, Esther N.M. Nolte-‘t Hoen, Alwin J. van der Ham, Arifa Ozir-Fazalalikhan, D. Linh Nguyen, Clarize M. de Korne, Roman I. Koning, John J. Tomes, Karl F. Hoffmann, Hermelijn H. Smits, Cornelis H. Hokke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (SciVal)
71 Downloads (Pure)

Abstract

Helminths like Schistosoma mansoni release excretory/secretory (E/S) products that modulate host immunity to enable infection. Extracellular vesicles (EVs) are among these E/S products, yet molecular mechanisms and functionality of S. mansoni EV interaction with host immune cells is unknown. Here we demonstrate that EVs released by S. mansoni schistosomula are internalised by human monocyte‐derived dendritic cells (moDCs). Importantly, we show that this uptake was mainly mediated via DC‐SIGN (CD209). Blocking DC‐SIGN almost completely abrogated EV uptake, while blocking mannose receptor (MR, CD206) or dendritic cell immunoreceptor (DCIR, CLEC4A) had no effect on EV uptake. Mass spectrometric analysis of EV glycans revealed the presence of surface N‐glycans with terminal Galβ1‐4(Fucα1‐3)GlcNAc (LewisX) motifs, and a wide array of fucosylated lipid‐linked glycans, including LewisX, a known ligand for DC‐SIGN. Stimulation of moDCs with schistosomula EVs led to increased expression of costimulatory molecules CD86 and CD80 and regulatory surface marker PD‐L1. Furthermore, schistosomula EVs increased expression of IL‐12 and IL‐10 by moDCs, which was partly dependent on the interaction with DC‐SIGN. These results provide the first evidence that glycosylation of S. mansoni EVs facilitates the interaction with host immune cells and reveals a role for DC‐SIGN and EV‐associated glycoconjugates in parasite‐induced immune modulation.
Original languageEnglish
Article number1753420
Number of pages19
JournalJournal of Extracellular Vesicles
Volume9
Issue number1
Early online date30 Apr 2020
DOIs
Publication statusPublished - 01 Sept 2020

Keywords

  • DC-SIGN
  • Extracellular vesicles
  • glycans
  • immune responses
  • Schistosoma mansoni

Fingerprint

Dive into the research topics of 'DC‐SIGN mediated internalisation of glycosylated extracellular vesicles from Schistosoma mansoni increases activation of monocyte‐derived dendritic cells'. Together they form a unique fingerprint.

Cite this