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

文献类型: 外文期刊

第一作者: Jin, Xuemin

作者: Jin, Xuemin;Yang, Yong;Ding, Jing;Liu, Xiaolei;Bai, Xue;Liu, Mingyuan;Shi, Haining;Luo, Xuenong;Jia, Wanzhong;Cai, Xuepeng;Vallee, Isabelle;Boireau, Pascal;Liu, Mingyuan

作者机构:

关键词: Trichinella spiralis; NLRP3; CD4(+)T cell; Th2 response; Host defense

期刊名称:VETERINARY PARASITOLOGY ( 影响因子:2.738; 五年影响因子:2.951 )

ISSN: 0304-4017

年卷期: 2021 年 297 卷

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收录情况: SCI

摘要: 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 wildtype (WT) CD4(+) T cells, the expression of IL-4 mRNA was reduced in NLRP3(-/-) CD4(+) T cells, however, the expression of IFN-gamma 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-gamma 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.

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