Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection

The endoparasite 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. Here we show that phytic acid is also present in E. multilocularis 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, IL-1ß, and TNF 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. Overall design: RNAseq of Mus musculus (C57BL/6JRj) livers that were orally infected with 1000 Echinococcus multilocularis eggs.