Borup, Anne, Sharifpour, Mohammad Farouq, Rossen, Litten S., Whitehead, Bradley, Boysen, Anders T., Olesen, Rikke, Bohn, Anja B., Ridolfi, Andrea, Brucale, Marco, Valle, Francesco, Paolini, Lucia, Radeghieri, Annalisa, Bergese, Paolo, Miles, Kim, Veitch, Margaret, Thomas, Tamara, Ruscher, Roland, Wangchuk, Phurpa, Giacomin, Paul, Loukas, Alex, and Nejsum, Peter (2025) Helminth extracellular vesicles co-opt host monocytes to drive T cell anergy. Journal of Extracellular Vesicles, 14 (1). e70027.

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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.

Item ID:	84585
Item Type:	Article (Research - C1)
ISSN:	2001-3078
Keywords:	Ascaris,colitis,extracellular vesicles,helminth,host-parasite interaction,immune modulation,inflammatory bowel disease,monocytes
Related URLs:	https://www.scopus.com/inward/record.uri...
Copyright Information:	© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
Funders:	National Health and Medical Research Council (NHMRC)
Projects and Grants:	NHMRC Investigator Grant (2008450)
Date Deposited:	11 Feb 2025 22:47
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