Up-regulation of MDP and tuftsin gene expression in Th1 and Th17 cells as an adjuvant for an oral Lactobacillus casei vaccine against anti-transmissible gastroenteritis virus
Up-regulation of MDP and tuftsin gene expression in Th1 and Th17 cells as an adjuvant for an oral Lactobacillus casei vaccine against anti-transmissible gastroenteritis virus
复制标题
作为抗传染性胃肠炎病毒口服干酪乳杆菌疫苗的佐剂，上调 Th1 和 Th17 细胞中的 MDP 和 tuftsin 基因表达
DOI：
10.1007/s00253-014-5893-2
复制
发表时间：
2014-10-01
影响因子：
5
通讯作者：
Li, Yijing
中科院分区：
文献类型：
--
作者：
Jiang, Xinpeng;Yu, Meiling;Li, Yijing
胞壁二肽(MDP)和Tuftsin在口服免疫调节中的作用尚不清楚，特别是在干酪乳杆菌(L.Casei)疫苗中。为了解决这一问题，我们研究了干酪乳杆菌表达的不同重复多肽，特别是重复20次和40次(20MT和40Mt)的MDP和Tuftsin融合蛋白(MT)，在同时表达传染性胃肠炎病毒S蛋白(S)D抗原位点的小鼠中对肠道和系统免疫反应的影响，并证实了这些多肽的免疫调节作用。用由表达MDP和tuftsin的干酪乳杆菌组成的不同疫苗治疗小鼠，可刺激体液和细胞免疫反应。用酶联免疫吸附试验检测，20MT和40MT均能诱导抗TGEV的Ig G和Ig A水平升高。增强的免疫球蛋白和免疫球蛋白A可激活体外的TGEV中和抗体活性。此外，20MT和40Mt可刺激天然免疫细胞分化，包括辅助性T细胞亚类和调节性T(Treg)细胞，从而分别诱导强大的辅助性T细胞1型和17型辅助性T细胞(Th17)应答，降低辅助性T细胞免疫应答。值得注意的是，用表达20MT和40MT的干酪乳杆菌处理小鼠，可以增强体液和粘膜免疫系统的抗TGEV抗体免疫反应。这些结果表明，表达MDP和Tuftsin的干酪乳杆菌具有显著的免疫增强作用，口服给药后可以诱导体液和T细胞介导的免疫应答，并可用于预防TGEV攻击的口服疫苗。
The role of muramyl dipeptide (MDP) and tuftsin in oral immune adjustment remains unclear, particularly in a Lactobacillus casei (L. casei) vaccine. To address this, we investigated the effects of different repetitive peptides expressed by L. casei, specifically the MDP and tuftsin fusion protein (MT) repeated 20 and 40 times (20MT and 40MT), in mice also expressing the D antigenic site of the spike (S) protein of transmissible gastroenteritis virus (TGEV) on intestinal and systemic immune responses and confirmed the immunoregulation of these peptides. Treatment of mice with a different vaccine consisting of L. casei expressing MDP and tuftsin stimulated humoral and cellular immune responses. Both 20MT and 40MT induced an increase in IgG and IgA levels against TGEV, as determined using enzyme-linked immunosorbent assay. Increased IgG and IgA resulted in the activation of TGEV-neutralising antibody activity in vitro. In addition, 20MT and 40MT stimulated the differentiation of innate immune cells, including T helper cell subclasses and regulatory T (Treg) cells, which induced robust T helper type 1 and T helper type 17 (Th17) responses and reduced Treg T cell immune responses in the 20MT and 40MT groups, respectively. Notably, treatment of mice with L. casei expressing 20MT and 40MT enhanced the anti-TGEV antibody immune responses of both the humoral and mucosal immune systems. These findings suggest that L. casei expressing MDP and tuftsin possesses substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration, and it may be useful in oral vaccines against TGEV challenge.