Joardar Nikhilesh, Bhattacharya Rajarshi, Halder Satyajit, Sen Animesh, Biswas Swadesh Ranjan, Jana Kuladip, Babu Santi Prasad Sinha
Parasitology Laboratory, Department of Zoology, Siksha Bhavana, Visva-Bharati, Santiniketan 731235, India.
Molecular Food Microbiology Laboratory, Department of Botany, Siksha Bhavana, Visva-Bharati, Santiniketan 731235, India.
Int J Biol Macromol. 2021 Dec 15;193(Pt B):1379-1390. doi: 10.1016/j.ijbiomac.2021.10.200. Epub 2021 Nov 10.
Lymphatic filariasis and its associated health hazards have taken enormous tolls especially in the tropical and sub-tropical countries round the globe. Our present work contemplates the immunomodulatory role of filarial Thioredoxin reductase (TrxR) for the survival of the parasite inside the human host. For this, the protein TrxR was purified from the filarial parasite Setaria cervi and further substantiated through specific anti-TrxR antibody raised in mice. Both commercially available anti-TrxR antibody and laboratory raised antibody produced a single band with a molecular mass of ~80 kDa on western blot. The protein is optimally active at pH 7.0 and at temperature 37 °C. This protein contains both alpha helix and beta pleated sheet with selenocysteine at its active site. The Km was found to be 2.75 ± 0.49 mM. TrxR was found to downregulate lipopolysaccharide (LPS)-induced inflammation in macrophages due to inhibition of TLR4-NF-κB pathway. The result was further supported by the downregulation of inflammasome pathway and activation of alternatively activated macrophages upon TrxR treatment. Hence this study projects insights into the importance of filarial TrxR in host-parasite interface as well as it illustrates novel therapeutic strategy towards anti-filarial drug development.
淋巴丝虫病及其相关的健康危害造成了巨大损失，尤其是在全球的热带和亚热带国家。我们目前的工作探讨了丝虫硫氧还蛋白还原酶（TrxR）在寄生虫于人类宿主体内存活中的免疫调节作用。为此，从丝状寄生虫鹿丝状线虫中纯化了TrxR蛋白，并通过在小鼠体内产生的特异性抗TrxR抗体进一步证实。市售抗TrxR抗体和实验室产生的抗体在蛋白质印迹上均产生了一条分子量约为80 kDa的单条带。该蛋白在pH 7.0和37°C温度下具有最佳活性。该蛋白同时包含α螺旋和β折叠片，其活性位点含有硒代半胱氨酸。发现Km为2.75±0.49 mM。由于抑制了TLR4-NF-κB途径，发现TrxR可下调巨噬细胞中脂多糖（LPS）诱导的炎症。TrxR处理后炎性小体途径的下调和交替激活的巨噬细胞的激活进一步支持了该结果。因此，本研究深入探讨了丝状TrxR在宿主-寄生虫界面中的重要性，同时也阐述了抗丝虫药物开发的新治疗策略。
