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Glycomolecules in Echinococcus granulosus cyst fluid inhibit TLR4-mediated inflammatory responses via c-Raf

Cellular & Molecular Immunology volume 17, pages 423–425 (2020)Cite this article

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Cystic echinococcosis, which is caused by larval infection of Echinococcus granulosus (E. granulosus) sensu lato, is a widespread chronic cyst-forming helminthic disease that affects up to 3 million people.1 E. granulosus can actively divert the host immune response towards anergy and anti-inflammatory pathways.2 Previous studies have shown that E. granulosus can escape host immunosurveillance by modulating the maturation of dendritic cells (DCs).3,4 Nevertheless, how E. granulosus, an extracellular pathogen, modulates the inflammatory response in DCs remains poorly understood. In this study, we investigated the effects of E. granulosus cyst fluid (EgCF) on bone marrow-derived DCs (BMDCs) exposed to LPS, an inflammatory stimulus, and the mechanisms involved in the EgCF–DCs immune modulation.

Some pathogens modulate Toll-like receptor (TLR) signaling via the c-Raf-acetylation-dependent pathway.6 Here, we found that BMDCs exposed to EgCF exhibited enhanced c-Raf phosphorylation, which could be decreased by GW5074,7 a selective c-Raf inhibitor (Fig. 1c). Following GW5074 treatment, the attenuated NF-κB p65 phosphorylation induced by EgCF was mostly restored to that of the LPS alone group (Fig. 1d). In addition, the TNF-α and IL-12 protein and mRNA levels were also restored to those observed under LPS single stimulation (Fig. 1e and Supplementary information, Fig. S2c), suggesting that EgCF impairs the TLR4-mediated inflammatory signaling pathway through c-Raf phosphorylation in the BMDCs.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81760371, 81760570, 81602810, 81703174), the XPCC Youth Science and Technology Innovation Leading Talent Program (2018CB017) and Key Areas of Science and Technology Projects (2019AB031).

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  1. These authors contributed equally: Jun Hou, Linlin Li, Dan Dong

Authors and Affiliations

  1. Department of Immunology, Shihezi University School of Medicine, Shihezi, Xinjiang, China

    Jun Hou, Linlin Li, Dan Dong, Lianghai Wang, Xian Wang, Kun Yang, Xiaodan Xu, Congzhe Chen & Xueling Chen

  2. Department of General Surgery, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China

    Xiangwei Wu

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  1. Jun Hou
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Contributions

X.C., J.H., L.L., and X.W. conceived the project. L.L., D.D., X.W., K.Y., X.X., and C.C. performed the experiments; L.L., L.W., J.H., X.W., and X.C. wrote and revised the manuscript.

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Correspondence to Xiangwei Wu or Xueling Chen.

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The authors declare no competing interests.

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Hou, J., Li, L., Dong, D. et al. Glycomolecules in Echinococcus granulosus cyst fluid inhibit TLR4-mediated inflammatory responses via c-Raf. Cell Mol Immunol 17, 423–425 (2020). https://doi.org/10.1038/s41423-019-0314-1

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