Jin Qi-Wang, Zhang Nian-Zhang, Li Wen-Hui, Qin Hong-Tao, Liu Yin-Ju, Ohiolei John Asekhaen, Niu Dong-Yu, Yan Hong-Bin, Li Li, Jia Wan-Zhong, Song Ming-Xin, Fu Bao-Quan
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Front Immunol. 2020 Sep 25;11:2015. doi: 10.3389/fimmu.2020.02015. eCollection 2020.
infection can induce macrophages into the alternatively activated phenotype, which is primarily associated with the development of a polarized Th2 immune response. In the present study, we examined the immunomodulatory effect of thioredoxin peroxidase-2 (TsTPX2), a protein derived from ES products, in the regulation of Th2 response through direct activation of macrophages. The location of TsTPX2 was detected by immunohistochemistry and immunofluorescence analyses. The immune response induced by rTsTPX2 was characterized by analyzing the Th2 cytokines and Th1 cytokines in the peripheral blood. The rTsTPX2-activated macrophages (M) were tested for polarization, their ability to evoke naïve CD4 T cells, and resistance to the larval infection after adoptive transfer in BALB/c mice. The immunolocalization analysis showed TsTPX2 in cuticles and stichosome of ML. The immunostaining was detected in cuticles and stichosome of Ad3 and ML, as well as in tissue-dwellings around ML after the intestines and muscle tissues of infected mice were incubated with anti-rTsTPX2 antibody. Immunization of BALB/c mice with rTsTPX2 could induce a Th1-suppressing mixed immune response given the increased levels of Th2 cytokines (IL-4 and IL-10) production along with the decreased levels of Th1 cytokines (IFN-γ, IL-12, and TNF-α). studies showed that rTsTPX2 could directly drive RAW264.7 and peritoneal macrophages to the M2 phenotype. Moreover, M could promote CD4 T cells polarized into Th2 type . Adoptive transfer of M into mice suppressed Th1 responses by enhancing Th2 responses and exhibited a 44.7% reduction in adult worm burden following challenge with infective larval, suggesting that the TsTPX2 is a potential vaccine candidate against trichinosis. Our study showed that TsTPX2 would be at least one of the molecules to switch macrophages into the M2 phenotype during infection, which provides a new therapeutic approach to various inflammatory disorders like allergies or autoimmune diseases.
感染可诱导巨噬细胞转变为替代性活化表型，这主要与极化的Th2免疫反应的发展相关。在本研究中，我们检测了硫氧还蛋白过氧化物酶-2（TsTPX2）（一种源自ES产物的蛋白质）通过直接激活巨噬细胞对Th2反应的调节作用。通过免疫组织化学和免疫荧光分析检测TsTPX2的定位。通过分析外周血中的Th2细胞因子和Th1细胞因子来表征rTsTPX2诱导的免疫反应。检测rTsTPX2激活的巨噬细胞（M）的极化情况、其激活初始CD4 T细胞的能力以及在BALB/c小鼠中过继转移后对幼虫感染的抵抗力。免疫定位分析显示TsTPX2存在于旋毛虫的角质层和杆状体中。在用抗rTsTPX2抗体孵育感染小鼠的肠道和肌肉组织后，在Ad3和旋毛虫的角质层和杆状体以及旋毛虫周围的组织驻留部位检测到免疫染色。用rTsTPX2免疫BALB/c小鼠可诱导Th1抑制性混合免疫反应，因为Th2细胞因子（IL-4和IL-10）的产生水平增加，同时Th1细胞因子（IFN-γ、IL-12和TNF-α）的水平降低。研究表明，rTsTPX2可直接将RAW264.7细胞和腹腔巨噬细胞驱动为M2表型。此外，M可促进CD4 T细胞极化为Th2型。将M过继转移到小鼠体内可通过增强Th2反应来抑制Th1反应，并且在用感染性幼虫攻击后成虫虫负荷降低了44.7%，这表明TsTPX2是抗旋毛虫病的潜在疫苗候选物。我们的研究表明，TsTPX2至少是感染期间将巨噬细胞转变为M2表型的分子之一，这为过敏或自身免疫性疾病等各种炎症性疾病提供了一种新的治疗方法。
