NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Parasit Vectors. 2023 Sep 23;16(1):334. doi: 10.1186/s13071-023-05947-2.
Interruption of parasite reproduction by targeting migrating schistosomula is a promising strategy for managing schistosomiasis. Hepatic schistosomula proteins previously identified based on second-generation schistosome DNA sequencing were found to hold excellent potential for schistosomiasis japonica diagnosis and as vaccine candidates. However, there are still many unknown schistosomula proteins that warrant further investigations. Herein, a novel schistosomula protein, the Schistosoma japonicum erythroid Krüppel-like factor (SjEKLF/KLF1), was explored.
Sequence alignment was carried out to detect the amino acid sequence characteristics of SjEKLF. The expression profile of SjEKLF was determined by western blot and immunofluorescence analysis. Enzyme-linked immunosorbent assay was used to determine the antigenicity of SjEKLF in hosts. Mice immunised with recombinant SjEKLF were challenged to test the potential value of the protein as an immunoprotective target.
SjEKLF is defined as EKLF/KLF1 for its C-terminal DNA-binding domain. SjEKLF is mainly expressed in hepatic schistosomula and male adults and located within the intestinal intima of the parasites. Notably, high levels of SjEKLF-specific antibodies were detected in host sera and SjEKLF exhibited outstanding sensitivity and specificity for schistosomiasis japonica immunodiagnosis but failed to distinguish between ongoing infection and previous exposure. In addition, SjEKLF immunisation reduced the infection in vivo, resulting in decreased worm and egg counts, and alleviated body weight loss and hepatomegaly in infected mice.
Overall, these findings demonstrate that SjEKLF is critical for the infection of S. japonicum and may be a potential target to help control S. japonicum infection and transmission.
通过靶向迁移的曼氏血吸虫童虫来阻断寄生虫的繁殖是一种很有前途的血吸虫病防治策略。先前基于第二代血吸虫 DNA 测序鉴定的肝期童虫蛋白被发现具有良好的日本血吸虫病诊断和疫苗候选物的潜力。然而,仍有许多未知的童虫蛋白需要进一步研究。在此,探索了一种新的童虫蛋白,日本血吸虫红细胞 Krüppel 样因子(SjEKLF/KLF1)。
进行序列比对以检测 SjEKLF 的氨基酸序列特征。通过 Western blot 和免疫荧光分析确定 SjEKLF 的表达谱。酶联免疫吸附试验用于测定宿主中 SjEKLF 的抗原性。用重组 SjEKLF 免疫小鼠,以测试该蛋白作为免疫保护靶标的潜在价值。
SjEKLF 因其 C 端 DNA 结合域而被定义为 EKLF/KLF1。SjEKLF 主要在肝期童虫和雄性成虫中表达,位于寄生虫的肠内膜内。值得注意的是,在宿主血清中检测到高水平的 SjEKLF 特异性抗体,SjEKLF 对日本血吸虫病免疫诊断具有出色的敏感性和特异性,但无法区分现症感染和既往暴露。此外,SjEKLF 免疫可减少体内感染,导致蠕虫和卵计数减少,并减轻感染小鼠的体重减轻和肝肿大。
总的来说,这些发现表明 SjEKLF 对 S. japonicum 的感染至关重要,可能是控制 S. japonicum 感染和传播的潜在靶标。