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, MA, USA.
Vet Res. 2020 Aug 27;51(1):107. doi: 10.1186/s13567-020-00829-2.
Trichinella spiralis maintains chronic infections within its host. Muscle larvae excretory-secretory products (MLES) typically induce parasite-specific immune responses such as the Th2 response and regulatory T cells (Tregs) by modulating dendritic cell (DC) phenotype via the recognition of pattern recognition receptors (PRRs), such as Nod-like receptors (NLRs). We aimed to investigate the role of NLRP3 in T. spiralis-triggered immune response. We found that larvae burden was increased in NLRP3 mice compared to wild type (WT) mice. Administration of MLES induced higher levels of IL-4, IL-10, TGF-β and population of Tregs in WT mice than in NLRP3 mice. In vitro, we showed that increased expression of CD40 on the surface of MLES-treated DCs was inhibited after NLRP3 knockout. Increased production of IL-1β, IL-18, IL-10 and TGF-β, but not IL-12p70, was significantly diminished in the absence of NLRP3. Furthermore, our results demonstrated that MLES-treated DCs induced higher levels of IL-4, IL-10 and TGF-β and populations of Tregs in vitro. These inductions were abolished by NLRP3 deficiency in DCs, suggesting that NLRP3 in MLES-treated DCs plays a role in promoting the Th2 and Treg response. Taken together, we identified for the first time the involvement of NLRP3 in host defences against T. spiralis.
旋毛虫在宿主体内维持慢性感染。肌肉幼虫排泄-分泌产物（MLES）通常通过识别模式识别受体（PRRs），如 Nod 样受体（NLRs），调节树突状细胞（DC）表型，诱导寄生虫特异性免疫反应，如 Th2 反应和调节性 T 细胞（Tregs）。我们旨在研究 NLRP3 在旋毛虫触发免疫反应中的作用。我们发现 NLRP3 小鼠的幼虫负担比野生型（WT）小鼠增加。与 NLRP3 小鼠相比，MLES 诱导 WT 小鼠产生更高水平的 IL-4、IL-10、TGF-β 和 Tregs 群体。在体外，我们表明，NLRP3 敲除后，MLES 处理的 DC 表面 CD40 的表达增加受到抑制。NLRP3 缺失后，IL-1β、IL-18、IL-10 和 TGF-β 的产生增加，但 IL-12p70 没有明显减少。此外，我们的结果表明，MLES 处理的 DC 在体外诱导更高水平的 IL-4、IL-10 和 TGF-β 和 Tregs 群体。在 DC 中缺乏 NLRP3 后，这些诱导被消除，表明 NLRP3 在 MLES 处理的 DC 中在促进 Th2 和 Treg 反应中发挥作用。总之，我们首次发现 NLRP3 参与宿主对旋毛虫的防御。
