Notch signaling pathway involved in Echinococcus granulosus infection regulates dendritic cell development and differentiation

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Junhu Hei¹  Xueling Ma¹  Mingxia Wang¹  Zailing Shang¹  Fei Qiao¹  Yana Wang² 

[1] Basic Medical Institute of Ningxia Medical University, Yinchuan, China;Basic Medical Institute of Ningxia Medical University, Yinchuan, China;Key Laboratory of Common Infectious Diseases of Ningxia Autonomous Region, Ningxia Medical University, Yinchuan, China;

关键词: Notch signal;    dendritic cell;    maturation;    antigen;    Echinococcus granulosus;    immune response;   

DOI  :  10.3389/fcimb.2023.1147025

 received in 2023-01-19, accepted in 2023-04-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe Notch signaling pathway is involved in the development of many diseases; it regulates the development of dendritic cells (DCs), and affects the immune response of DC-mediated T cells. We previously found that ferritin and malate dehydrogenase (mMDH) in Echinococcus granulosus (E.granulosus) induced different immune responses through sensitized DCs. Therefore, in the study we explored whether the Notch signaling pathway affects the development and differentiation of DCs, causing changes in the immune response of DCs sensitized with E. granulosus antigens, and clarified whether it is involved in E.granulosus infection. MethodsWe used the Notch signaling pathway inhibitor [N-[3,5-difluorophenace-tyl] -L-alanyl]-S-phenylglycinet-butyl ester (DAPT) or activator Jagged1 to construct in vitro cell models with blocked or activated Notch signaling respectively. We analyzed the effect of Notch signaling on the development and differentiation of DCs by detecting their morphology, migration function, capacity to promote T cell proliferation, and cytokine secretion. We observed the changes in DC response to E. granulosus antigens and the mediated immune response. ResultsDAPT inhibited the development and maturation of DCs, which were in a non-responsive or incompetent state, reduced the sensitization of DCs to Eg.ferritin, weakened the migration ability of DCs, disrupted their ability to mediate T-cell proliferation, reduced DC expression of MHCII, CD80, CD60, and CD40 co-stimulatory molecules, prevented the secretion of cytokines and attenuated the expression of Notch1, Notch2, Notch3 receptors, Jagged1, Delta-like 4 (Delta4), and Hes1. Following Jagged1 addition, the function of DCs was restored to some extent, and the expression of Notch1, Delta4 and Hes1 was activated in response to the stimulation of Eg.ferritin. However, Eg.mMDH stimulated DCs to produce an immune response showing weak interference by DAPT and Jagged1.DiscussionThe study suggests that the Notc h signaling pathway is involved in the Eg.ferritin-sensitized DC-mediated immune response, which may become a new target for treating E.granulosus infection.

【 授权许可】

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Copyright © 2023 Wang, Shang, Qiao, Hei, Ma and Wang