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Nod-样受体含pyrin 结构域蛋白 3 在 Th2 细胞介导的抗旋毛虫感染的宿主防御反应的发展中起着关键作用。

Nod-like receptor pyrin domain containing 3 plays a key role in the development of Th2 cell-mediated host defenses against Trichinella spiralis infection.

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.

Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, United States.

出版信息

Vet Parasitol. 2021 Sep;297:109159. doi: 10.1016/j.vetpar.2020.109159. Epub 2020 Jun 1.

DOI:10.1016/j.vetpar.2020.109159
PMID:32564937
Abstract

The inflammasome is a key line of immune defense against invading infectious pathogens. However, knowledge of the role of nod-like receptor pyrin domain containing 3 (NLRP3) in Trichinella spiralis infection which characteristically induces T-helper 2 (Th2) immune responses is sparse. In this study, we investigated the role of NLRP3 in the protection against T. spiralis infection through the Th2 immune response. We show that NLRP3 expression in CD4 T cells was significantly increased at 7 days post-infection of T. spiralis. Compared to wild-type (WT) CD4 T cells, the expression of IL-4 mRNA was reduced in NLRP3 CD4 T cells, however, the expression of IFN-γ mRNA was comparable between the two groups. Consistently, ELISA and flow cytometry analysis showed that NLRP3 CD4 T cells secreted lower levels of IL-4 than CD4 T cells from WT mice, whilst the levels of IFN-γ secreted by NLRP3 CD4 T cells were of similar levels to those secreted by WT CD4 T cells. In addition, we observed a significant reduction of IL-4 and IL-13 by ELISA in NLRP3 mice at 1, 2 and 4 weeks post-infection. Furthermore, we found that adult worm survival was substantially prolonged and muscle larvae burden was significantly increased in NLRP3 mice. We further show that NLRP3 promotes the host defense against T. spiralis through its participation in the differentiation of Th2 cells. These findings provide novel insights into parasite expulsion and highlight the importance of NLRP3 in the host defense against T. spiralis.

摘要

炎症小体是针对入侵性传染性病原体的主要免疫防御线。然而,对于旋毛虫感染中 NOD 样受体富含亮氨酸重复结构域 3(NLRP3)的作用知之甚少,旋毛虫感染特征性地诱导辅助性 T 细胞 2(Th2)免疫反应。在这项研究中,我们通过 Th2 免疫反应研究了 NLRP3 在保护抵抗旋毛虫感染中的作用。我们发现,感染旋毛虫后第 7 天,CD4 T 细胞中的 NLRP3 表达显著增加。与野生型(WT)CD4 T 细胞相比,NLRP3 CD4 T 细胞中 IL-4 mRNA 的表达减少,然而,两组之间 IFN-γ mRNA 的表达相当。一致地,ELISA 和流式细胞术分析表明,NLRP3 CD4 T 细胞分泌的 IL-4 水平低于 WT 小鼠的 CD4 T 细胞,而 NLRP3 CD4 T 细胞分泌的 IFN-γ 水平与 WT CD4 T 细胞分泌的 IFN-γ 水平相当。此外,我们观察到 NLRP3 小鼠在感染后 1、2 和 4 周时,IL-4 和 IL-13 的 ELISA 水平显著降低。此外,我们发现,NLRP3 小鼠中的成虫存活时间显著延长,肌肉幼虫负担显著增加。我们进一步表明,NLRP3 通过参与 Th2 细胞的分化来促进宿主对旋毛虫的防御。这些发现为寄生虫排出提供了新的见解,并强调了 NLRP3 在宿主防御旋毛虫中的重要性。

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