Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection

Abstract The helminth Echinococcus multilocularis relies on immune evasion strategies to persist within its host. The laminated layer (LL) surrounding the parasite provides physical protection while modulating host immune responses. E. multilocularis’ immunomodulatory mechanisms are poorly understoo...

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Main Authors: Manuel Salzmann, Ulrike Resch, Laura Boccuni, Carina Schneider, Elena T. Pichler, Mira Brekalo, Pavel Uhrin, Philipp A. Kronenberg, Marion Wassermann, Thomas Romig, Johann Wojta, Philipp J. Hohensinner
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08283-6
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author Manuel Salzmann
Ulrike Resch
Laura Boccuni
Carina Schneider
Elena T. Pichler
Mira Brekalo
Pavel Uhrin
Philipp A. Kronenberg
Marion Wassermann
Thomas Romig
Johann Wojta
Philipp J. Hohensinner
author_facet Manuel Salzmann
Ulrike Resch
Laura Boccuni
Carina Schneider
Elena T. Pichler
Mira Brekalo
Pavel Uhrin
Philipp A. Kronenberg
Marion Wassermann
Thomas Romig
Johann Wojta
Philipp J. Hohensinner
author_sort Manuel Salzmann
collection DOAJ
description Abstract The helminth Echinococcus multilocularis relies on immune evasion strategies to persist within its host. The laminated layer (LL) surrounding the parasite provides physical protection while modulating host immune responses. E. multilocularis’ immunomodulatory mechanisms are poorly understood and we explored the role of phytic acid, a known component of E. granulosus sensu lato. We show that phytic acid is also present in E. multilocularis-infected tissue and impairs macrophage inflammation. In vivo, inflammatory macrophages accumulate near the metacestode, yet do not express IL-6, indicating anti-inflammatory modulation. In vitro, phytic acid reduces pro-inflammatory cytokines such as IL-6 and IL-1β by lowering intracellular calcium levels in macrophages. This calcium-chelating effect is mirrored by the anti-inflammatory properties of an E. multilocularis metacestode extract, revealing a protein-independent immune modulation strategy. These findings suggest that phytic acid plays a crucial role in E. multilocularis’ ability to suppress host immune responses and supports the parasite’s long-term survival.
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spelling doaj-art-880b5ee2149b4a9ca2080157ba6fef792025-08-20T02:05:42ZengNature PortfolioCommunications Biology2399-36422025-06-018111110.1038/s42003-025-08283-6Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infectionManuel Salzmann0Ulrike Resch1Laura Boccuni2Carina Schneider3Elena T. Pichler4Mira Brekalo5Pavel Uhrin6Philipp A. Kronenberg7Marion Wassermann8Thomas Romig9Johann Wojta10Philipp J. Hohensinner11Department of Internal Medicine II/Cardiology, Medical University of Vienna, Währinger Gürtel 18-20Institute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17Department of Internal Medicine II/Cardiology, Medical University of Vienna, Währinger Gürtel 18-20University of Hohenheim, Parasitology Unit, Emil-Wolff-Straße 34Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Währinger Gürtel 18-20Department of Internal Medicine II/Cardiology, Medical University of Vienna, Währinger Gürtel 18-20Institute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17Institute of Parasitology, University of Zurich, Winterthurerstrasse 266aUniversity of Hohenheim, Parasitology Unit, Emil-Wolff-Straße 34University of Hohenheim, Parasitology Unit, Emil-Wolff-Straße 34Department of Internal Medicine II/Cardiology, Medical University of Vienna, Währinger Gürtel 18-20Ludwig Boltzmann Institute for Cardiovascular Research, Währinger Gürtel 18-20Abstract The helminth Echinococcus multilocularis relies on immune evasion strategies to persist within its host. The laminated layer (LL) surrounding the parasite provides physical protection while modulating host immune responses. E. multilocularis’ immunomodulatory mechanisms are poorly understood and we explored the role of phytic acid, a known component of E. granulosus sensu lato. We show that phytic acid is also present in E. multilocularis-infected tissue and impairs macrophage inflammation. In vivo, inflammatory macrophages accumulate near the metacestode, yet do not express IL-6, indicating anti-inflammatory modulation. In vitro, phytic acid reduces pro-inflammatory cytokines such as IL-6 and IL-1β by lowering intracellular calcium levels in macrophages. This calcium-chelating effect is mirrored by the anti-inflammatory properties of an E. multilocularis metacestode extract, revealing a protein-independent immune modulation strategy. These findings suggest that phytic acid plays a crucial role in E. multilocularis’ ability to suppress host immune responses and supports the parasite’s long-term survival.https://doi.org/10.1038/s42003-025-08283-6
spellingShingle Manuel Salzmann
Ulrike Resch
Laura Boccuni
Carina Schneider
Elena T. Pichler
Mira Brekalo
Pavel Uhrin
Philipp A. Kronenberg
Marion Wassermann
Thomas Romig
Johann Wojta
Philipp J. Hohensinner
Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
Communications Biology
title Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
title_full Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
title_fullStr Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
title_full_unstemmed Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
title_short Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection
title_sort phytic acid impairs macrophage inflammatory response in echinococcus multilocularis infection
url https://doi.org/10.1038/s42003-025-08283-6
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