Helminth extracellular vesicles co-opt host monocytes to drive T cell anergy

Anne Borup*, Mohammad Farouq Sharifpour*, Litten S. Rossen, Bradley Whitehead, Anders T. Boysen, Rikke Olesen, Anja B. Bohn, Andrea Ridolfi, Marco Brucale, Francesco Valle, Lucia Paolini, Annalisa Radeghieri, Paolo Bergese, Kim Miles, Margaret Veitch, Tamara Thomas, Roland Ruscher, Phurpa Wangchuk, Paul Giacomin, Alex LoukasPeter Nejsum*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Parasitic helminths secrete extracellular vesicles (EVs) into their host tissues to modulate immune responses, but the underlying mechanisms are poorly understood. We demonstrate that Ascaris EVs are efficiently internalised by monocytes in human peripheral blood mononuclear cells and increase the percentage of classical monocytes. Furthermore, EV treatment of monocytes induced a novel anti-inflammatory phenotype characterised by CD14+, CD16, CC chemokine receptor 2 (CCR2) and programmed death-ligand 1 (PD-L1)+ cells. In addition, Ascaris EVs induced T cell anergy in a monocyte-dependent mechanism. Targeting professional phagocytes to induce both direct and indirect pathways of immune modulation presents a highly novel and efficient mechanism of EV-mediated host-parasite communication. Intra-peritoneal administration of EVs induced protection against gut inflammation in the dextran sodium sulphate model of colitis in mice. Ascaris EVs were shown to affect circulating immune cells and protect against gut inflammation; this highlights their potential as a subject for further investigation in inflammatory conditions driven by dysregulated immune responses. However, their clinical translation would require further studies and careful consideration of ethical implications.

Original languageEnglish
Article numbere70027
Pages (from-to)1-18
Number of pages18
JournalJournal of Extracellular Vesicles
Volume14
Issue number1
Early online date16 Jan 2025
DOIs
Publication statusPublished - Jan 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

Keywords

  • Ascaris
  • colitis
  • extracellular vesicles
  • helminth
  • host-parasite interaction
  • immune modulation
  • inflammatory bowel disease
  • monocytes

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