NLRP3 Plays a Key Role in Antihelminth Immunity in the Enteral and Parenteral Stages of Trichinella spiralis-Infected Mice

Autor: Tian-Xu Pan, Hai-Bin Huang, Hui-Nan Lu, Guang-Xun Zhao, Yu Quan, Jun-Yi Li, Ying Xue, Zhi-Yu Zhu, Yue Wang, Chun-Wei Shi, Nan Wang, Gui-Lian Yang, Chun-Feng Wang
Rok vydání: 2023
Předmět:
Zdroj: Infection and Immunity. 91
ISSN: 1098-5522
0019-9567
DOI: 10.1128/iai.00382-22
Popis: Background: Trichinellosis is an important food-borne zoonosis, and no effective treatments are yet available. Nod-like receptor plays a critical role in the host response against nematodes. Therefore, we aimed to explore the role of the NLRP3 inflammasome (NLRP3) during the adult, migrating, and encysted stages of Trichinella spiralis (T. spiralis) infection. Methods: The mice were treated with the specific NLRP3 inhibitor MCC950 after inoculation with T. spiralis. Then, NLRP3 plays the role in T. spiralis-infected mice were evaluated using ELISA, Western blotting, Flow cytometry, Histopathological evaluation, Bone marrow-derived macrophage (BMDM) stimulation and immunofluorescenceResults: The in vivo results showed that NLRP3 enhanced the Th1 immune response in the adult stage and the migrating stage and weakened the Th2 immune response in the encysted stage. NLRP3 promoted the release of proinflammatory factors (INF-γ) and suppressed the release of anti-inflammatory factors (IL-4). Pathological changes were also improved in the absence of NLRP3 in mice during T. spiralis infection. Importantly, a significant reduction in adult worm burden and muscle larvae burden at 7 and 35 days post infection was observed in mice treated with the specific NLRP3 inhibitor MCC950. In vitro, we first demonstrated that NLRP3 in macrophages can be activated by T. spiralis proteins and promotes IL-1β and IL-18 release. Conclusions: This study revealed that the NLRP3 is involved in the host response to T. spiralis infection and that targeted inhibition of NLRP3 enhanced the Th2 response and accelerated T. spiralis expulsion. These findings may help in the development of protocols for controlling trichinellosis.
Databáze: OpenAIRE
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