Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Muhammad Tahir Aleem; Zhaohai Wen; Zhengqing Yu; Cheng Chen; Mingmin Lu; Lixin Xu; Xiaokai Song; Xiangrui Li; Ruofeng Yan

doi:10.3390/vaccines11091437

Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden

Vaccines (Basel). 2023 Aug 31;11(9):1437. doi: 10.3390/vaccines11091437.

Authors

Muhammad Tahir Aleem^{1

2}, Zhaohai Wen¹, Zhengqing Yu³, Cheng Chen¹, Mingmin Lu¹, Lixin Xu¹, Xiaokai Song¹, Xiangrui Li¹, Ruofeng Yan¹

Affiliations

¹ MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
² Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, Cleveland, OH 44115, USA.
³ School of Agriculture, Ningxia University, Yinchuan 750021, China.

Abstract

Trichinella spiralis (T. spiralis), a nematode parasite, is the major cause of Trichinellosis, a zoonotic disease. A key role of MAPR in the reproductive system is to maintain pregnancy. Previous studies found that antihormone drug design and vaccine therapy of recombinant protein (rTs-MAPRC2) control T. spiralis infection. The current study investigates the inhibitory effects of different ratios of antibodies against Ts-MAPRC2 on the development of muscle larvae (ML) and newborn larvae (NBL). First, we performed indirect immunofluorescence assays and examined the effects of rTs-MAPRC2-Ab on ML and NBL in vitro as well as in vivo. Afterward, siRNA-Ts-MAPRC2 was transfected into T. spiralis muscle larvae. Following that, Ts-MAPRC2 protein was detected by Western Blotting, and mRNA levels were determined by qPCR. We also assessed whether siRNA-treated NBLs were infective by analyzing muscle larvae burden (MLs). Our results showed that rTs-MAPRC2-Ab greatly inhibited the activity of the Ts-MAPRC2 in ML and NBL of T. spiralis and rTs-MAPRC2-Ab reduced larval infectivity and survival in the host in a dose-dependent manner (1:50, 1:200, 1:800 dilutions). Furthermore, siRNA-Ts-MAPRC2 effectively silenced the Ts-MAPRC2 gene in muscle larvae (ML) in vitro, as well as in newborn larvae (NBL) of T. spiralis in vivo. In addition, siRNA-Ts-MAPRC2 (siRNA180, siRNA419, siRNA559) reduced host larval survival and infectivity significantly. This study, therefore, suggests that Ts-MAPRC2 might be a novel molecular target useful in the development of vaccines against T. spiralis infection.

Keywords: Trichinella spiralis; inhibitory effect; knockdown; rTs-MAPRC2-Ab; worm burden.

Grants and funding

This work was supported by the Social Development Project of Jiangsu Province (BE2022848) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).