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Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection

ABSTRACT: 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-1β, 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE278225 | GEO | 2025/06/12

REPOSITORIES: GEO

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Project description:The low phytic acid trait in soybeans can be conferred by loss-of-function mutations in genes encoding myo-inositol phosphate synthase and two epistatically interacting genes encoding multidrug-resistance protein ABC transporters. However, perturbations in phytic acid biosynthesis are associated with poor seed vigor. Since the benefits of the low phytic acid trait, in terms of end-use quality and sustainability, far outweigh the negatives associated with poor seed performance, a fuller understanding of the molecular basis behind the negatives will assist crop breeders and engineers in producing variates with low phytic acid and better germination rate. The gene regulatory network for developing low and normal phytic acid soybean seeds was previously constructed, with genes modulating a variety of processes pertinent to phytic acid metabolism and seed viability being identified. In this study, a comparative time series analysis of low and normal phytic acid soybeans was carried out to investigate the transcriptional regulatory elements governing the transitional dynamics from dry seed to germinated seed. Gene regulatory networks were reverse engineered from time series transcriptomic data of three distinct genotypic subsets composed of low phytic acid soybean lines and their normal phytic acid sibling lines. Using a robust unsupervised network inference scheme, putative regulatory interactions were inferred for each subset of genotypes. These interactions were further validated by published regulatory interactions found in Arabidopsis thaliana and motif sequence analysis. Results indicate that low phytic acid seeds have increased sensitivity to stress, which could be due to changes in phytic acid levels, disrupted inositol phosphate signaling, disrupted phosphate ion homeostasis, and altered myo-inositol metabolism. Putative regulatory interactions were identified for the latter two processes. Changes in abscisic acid signaling candidate transcription factors putatively regulating genes in this process were identified as well. Analysis of the gene regulatory networks reveal altered regulation in processes that may be affecting the germination of low phytic acid soybean seeds. Therefore, this work contributes to the ongoing effort to elucidate molecular mechanisms underlying altered seed viability, germination and field emergence of low phytic acid crops, understanding of which is necessary in order to mitigate these problems.

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Phytic acid impairs macrophage inflammatory response in Echinococcus multilocularis infection

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