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用旋毛虫C型凝集素对小鼠进行疫苗接种可引发保护性免疫并增强肠道上皮屏障功能。

Vaccination of mice with Trichinella spiralis C-type lectin elicited the protective immunity and enhanced gut epithelial barrier function.

作者信息

Wang Bo Ning, Zhang Xin Zhuo, Wu Jin Yi, Zhang Zhao Yu, Cong Pei Kun, Zheng Wen Wen, Long Shao Rong, Liu Ruo Dan, Cui Jing, Wang Zhong Quan

机构信息

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

出版信息

PLoS Negl Trop Dis. 2025 Jan 22;19(1):e0012825. doi: 10.1371/journal.pntd.0012825. eCollection 2025 Jan.

Abstract

BACKGROUND

C-type lectin (CTL) plays an important act in parasite adhesion, host's cell invasion and immune escape. Our previous studies showed that recombinant Trichinella spiralis C-type lectin (rTsCTL) mediated larval invasion of enteral mucosal epithelium. The aim of this study was to investigate protective immunity produced by vaccination with rTsCTL and its effect on gut epithelial barrier function in a mouse model.

METHODOLOGY/PRINCIPAL FINDING: The ELISA results showed that subcutaneous vaccination of mice with rTsCTL elicited a systemic humoral response (high levels of serum IgG, IgG1/IgG2a and IgA) and significant gut mucosal sIgA responses. The levels of Th1/Th2 cytokines (IFN-γ/IL-4) secreted from spleen, mesenteric lymph nodes and Peyer's patches were distinctly increased at 6 weeks following vaccination (P < 0.05). At one week after challenge, the numbers of goblet cells and expression level of Muc2, Muc5ac and pro-inflammatory cytokines (TNF-α and IL-1β) in gut tissues of vaccinated mice were obviously decreased, while expression of anti-inflammatory cytokines (IL-4 and IL-10) was evidently increased, compared to the infected PBS group. It is interesting that expression levels of gut epithelial tight junctions (TJs; occludin, claudin-1 and E-cad) were prominently elevated and intestinal permeability was interestingly declined in vaccinated mice. The rTsCTL-vaccinated mice exhibited a 51.69 and 48.19% reduction of intestinal adult and muscle larva burdens, respectively. The female fecundity in rTsCTL vaccinated mice was reduced by 40.51%. These findings indicated that rTsCTL vaccination impeded larval invasion and improved gut epithelial integrity and barrier function, reduced worm burdens, and relieved gut and muscle inflammation.

CONCLUSIONS

Vaccination of mice with rTsCTL elicited an obvious protective immunity against larval challenge, impeded larval invasion of gut mucosa, enhanced gut epithelial integrity and barrier function, reduced worm burdens; it also alleviated gut and muscle inflammation. TsCTL might be a novel candidate target molecule for anti-Trichinella vaccines.

摘要

背景

C型凝集素(CTL)在寄生虫黏附、宿主细胞侵袭及免疫逃逸过程中发挥重要作用。我们之前的研究表明,重组旋毛虫C型凝集素(rTsCTL)介导幼虫对肠黏膜上皮的侵袭。本研究旨在探讨用rTsCTL疫苗接种在小鼠模型中产生的保护性免疫及其对肠道上皮屏障功能的影响。

方法/主要发现:ELISA结果显示,用rTsCTL对小鼠进行皮下接种可引发全身性体液反应(血清IgG、IgG1/IgG2a和IgA水平升高)以及显著的肠道黏膜sIgA反应。接种后6周,脾脏、肠系膜淋巴结和派尔集合淋巴结分泌的Th1/Th2细胞因子(IFN-γ/IL-4)水平明显升高(P<0.05)。与感染PBS组相比,在攻击后1周,接种疫苗小鼠肠道组织中杯状细胞数量以及Muc2、Muc

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce9/11761079/ebfca01e6eae/pntd.0012825.g001.jpg

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