NLRP3 played a role in Trichinella spiralis -triggered Th2 and regulatory T cells response
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RESEARCH ARTICLE
Open Access
NLRP3 played a role in Trichinella spiralis‑triggered Th2 and regulatory T cells response Xuemin Jin1†, Xue Bai1†, Yong Yang1†, Jing Ding1, Haining Shi2, Baoquan Fu3, Pascal Boireau4, Mingyuan Liu1,5* and Xiaolei Liu1*
Abstract 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. Keywords: Trichinella spiralis, excretory-secretory products, dendritic cell, NLRP3, Th2, Treg Introduction Parasitic diseases are a serious global health concern. Trichinellosis, caused by Trichinella spiralis, is one of the most prevalent neglected tropical diseases worldwide, and establishes chronic infection in a wide range of wild and domestic animals and human beings [1]. T. spiralis infection induces strong T helper 2 (Th2) immune response [2], which contributes equally to host defence against T. spiralis [3]. And Th2 cytokines production is regulated by regulatory T cells (Tregs) [4]. *Correspondence: [email protected]; [email protected] † Xuemin Jin, Xue Bai and Yong Yang contributed equally to the work 1 Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China Full list of author information is available at the end of the article
Parasite antigens have the potential to induce Th2 and Treg responses via dendritic cells (DCs). Indeed, DCs have numerous pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) or nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) [5]. T. spiralis muscle larvae excretory-secretory products (MLESs) enable the parasite to survive in the host by interacting with host immune cells and inducing an immune response [6]. T. spiralis MLESs direct the immunological balance away from Th1 cells towar
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