The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

作者：Ning Xu, Xue Bai, Yan Liu, Yaming Yang, Bin Tang, Hai Ning Shi, Isabelle Vallée, Pascal Boireau, Xiaolei Liu, Mingyuan Liu · 发表于：The Journal of Immunology · 年份：2021 · DOI：10.4049/jimmunol.2000290 · 被引用次数：39 · 研究领域：Parasitic Diseases Research and Treatment、Immune responses and vaccinations、Parasites and Host Interactions

Abstract Trichinella spiralis is recognized for its ability to regulate host immune responses via excretory/secretory (ES) products. Serine protease inhibitors (serpins) play an important role in ES product-mediated immunoregulatory effects during T. spiralis infection. In this study, the immunoregulatory properties of a serpin derived from T. spiralis (Ts-serpin) were explored in BALB/c mice. The results showed that naturally occurring Ts-serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant Ts-serpin [rTs-serpin]) or blocking (by passive immunization with anti–rTs-serpin serum) the effects of Ts-serpin changed the levels of cytokines related to inflammation induced by T. spiralis infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early T. spiralis infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to Ts-serpin–mediated immunoregulation. Furthermore, a STAT6 activation mechanism independent of IL-4Rα has been found to regulate protein-mediated alternative activation of bone marrow–derived macrophages and mimic the immunoregulatory role of Ts-serpin in T. spiralis infection. Finally, the anti-inflammatory properties of rTs-serpin and bone marrow–derived macrophage alternative activation by rTs-serpin were demonstrated using a trinitrobenzene sulfonic acid–induced inflammat...