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口服减毒沙门氏菌编码弹性蛋白酶可诱导抗旋毛虫感染的保护性免疫。

Oral immunization with attenuated Salmonella encoding an elastase elicits protective immunity against Trichinella spiralis infection.

机构信息

Department of Parasitology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450052, China.

Department of Parasitology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450052, China.

出版信息

Acta Trop. 2022 Feb;226:106263. doi: 10.1016/j.actatropica.2021.106263. Epub 2021 Dec 5.

Abstract

Elastase belongs to the serine protease family. Previous studies showed that Trichinella spiralis elastase (TsE) was highly expressed in intestinal infective larvae (IIL). Recombinant TsE (rTsE) promoted the larval intrusion of enteral epithelium cells (IECs), whereas anti-rTsE antibodies and siRNA impeded larval intrusion. Subcutaneous vaccination of mice with rTsE showed a partial protective immunity, suggesting that TsE might be a promising vaccine target against Trichinella infection. In this study, complete TsE cDNA sequence was cloned into pcDNA3.1, and the rTsE DNA was transformed into attenuated S. typhimurium strain ΔcyaSL1344. Oral vaccination of mice with TsE DNA elicited a systemic Th1/Th2/Treg mixed immune response and gut local mucosal sIgA response. Immunized mice exhibited a significant immune protection against T. spiralis larval challenge, as demonstrated by a 52.48% reduction of enteral adult worms and a 69.43% reduction of muscle larvae. The protection might be related to the TsE-induced production of intestinal mucus, specific anti-TsE sIgA and IgG, and secretion of IFN-γ, IL-2, IL-4 and IL-10, which protected gut mucosa from larval intrusion, suppressed worm development and impeded female reproduction. The results demonstrated that attenuated Salmonella-delivered TsE DNA vaccine provided a prospective strategy for the control of Trichinella infection in food animals.

摘要

弹性蛋白酶属于丝氨酸蛋白酶家族。先前的研究表明,旋毛虫弹性蛋白酶(TsE)在肠道感染性幼虫(IIL)中高度表达。重组 TsE(rTsE)促进幼虫侵入肠上皮细胞(IECs),而抗 rTsE 抗体和 siRNA 则阻碍幼虫侵入。用 rTsE 对小鼠进行皮下接种显示出部分保护免疫力,表明 TsE 可能是一种有前途的针对旋毛虫感染的疫苗靶标。在这项研究中,完整的 TsE cDNA 序列被克隆到 pcDNA3.1 中,rTsE DNA 被转化到减毒鼠伤寒沙门氏菌ΔcyaSL1344 中。用 TsE DNA 对小鼠进行口服接种可引起全身性 Th1/Th2/Treg 混合免疫反应和肠道局部黏膜 sIgA 反应。免疫接种的小鼠对旋毛虫幼虫攻击表现出显著的免疫保护作用,肠道成虫减少 52.48%,肌肉幼虫减少 69.43%。这种保护可能与 TsE 诱导的肠道黏液产生、特异性抗 TsE sIgA 和 IgG 以及 IFN-γ、IL-2、IL-4 和 IL-10 的分泌有关,这些物质保护肠道黏膜免受幼虫侵入、抑制蠕虫发育和阻碍雌性繁殖。结果表明,减毒沙门氏菌递送的 TsE DNA 疫苗为控制食品动物中的旋毛虫感染提供了一种有前景的策略。

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