College of Veterinary Medicine, Hebei Agricultural University, Baoding, 071000, Hebei, China.
Department of Biochemistry and Molecular Biology, Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, 050200, Hebei, China.
Sci Rep. 2020 Nov 25;10(1):20530. doi: 10.1038/s41598-020-77551-8.
Enterotoxigenic Escherichia coli (ETEC), an essential cause of post-weaning diarrhea (PWD) in piglets, leads to significant economic losses to the pig industry. The present study aims to identify the role of ETEC total RNA in eliciting immune responses to protect animals against ETEC infection. The results showed that the total RNA isolated from pig-derived ETEC K88ac strain effectively stimulated the IL-1β secretion of porcine intestinal epithelial cells (IPEC-J2). The mouse model immunized with ETEC total RNA via intramuscular injection (IM) or oral route (OR) was used to evaluate the protective efficiency of the ETEC total RNA. The results suggested that 70 μg ETEC total RNA administered by either route significantly promoted the production of the serum IL-1β and K88ac specific immunoglobulins (IgG, IgM, and IgA). Besides, the ETEC RNA administration augmented strong mucosal immunity by elevating K88ac specific IgA level in the intestinal fluid. Intramuscularly administered RNA induced a Th1/Th2 shift toward a Th2 response, while the orally administered RNA did not. The ETEC total RNA efficiently protected the animals against the ETEC challenge either by itself or as an adjuvant. The histology characterization of the small intestines also suggested the ETEC RNA administration protected the small intestinal structure against the ETEC infection. Particularly of note was that the immunity level and protective efficacy caused by ETEC RNA were dose-dependent. These findings will help understand the role of bacterial RNA in eliciting immune responses, and benefit the development of RNA-based vaccines or adjuvants.
肠产毒性大肠杆菌（ETEC）是导致仔猪断奶后腹泻（PWD）的主要原因，给养猪业造成了巨大的经济损失。本研究旨在确定 ETEC 总 RNA 在引发免疫反应中的作用，以保护动物免受 ETEC 感染。研究结果表明，从猪源 ETEC K88ac 株中分离的总 RNA 能有效刺激猪肠上皮细胞（IPEC-J2）分泌 IL-1β。通过肌肉注射（IM）或口服途径（OR）用 ETEC 总 RNA 免疫的小鼠模型用于评估 ETEC 总 RNA 的保护效率。结果表明，两种途径给予 70μg ETEC 总 RNA 均可显著促进血清 IL-1β和 K88ac 特异性免疫球蛋白（IgG、IgM 和 IgA）的产生。此外，ETEC RNA 给药通过提高肠液中 K88ac 特异性 IgA 水平增强了强烈的黏膜免疫。肌肉内给予的 RNA 诱导了 Th1/Th2 向 Th2 反应的转变，而口服给予的 RNA 则没有。ETEC 总 RNA 无论是单独使用还是作为佐剂都能有效地保护动物免受 ETEC 攻毒。小肠的组织学特征也表明，ETEC RNA 给药可保护小肠结构免受 ETEC 感染。值得注意的是，ETEC RNA 引起的免疫水平和保护效力是剂量依赖性的。这些发现将有助于了解细菌 RNA 在引发免疫反应中的作用，并有助于 RNA 疫苗或佐剂的开发。
