Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.

<h4>Background</h4>To achieve sustainable and integrated control of schistosomiasis, it necessitates the implementation of comprehensive strategies, where effective vaccines could play a pivotal role. The limited identification and validation of schistosome antigens hinders the progress...

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Main Authors: Xianyu Piao, Yuanlong Wang, Ning Jiang, Pengfei Cai, Jiamei Duan, Shuai Liu, Qijun Chen, Nan Hou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0013241
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author Xianyu Piao
Yuanlong Wang
Ning Jiang
Pengfei Cai
Jiamei Duan
Shuai Liu
Qijun Chen
Nan Hou
author_facet Xianyu Piao
Yuanlong Wang
Ning Jiang
Pengfei Cai
Jiamei Duan
Shuai Liu
Qijun Chen
Nan Hou
author_sort Xianyu Piao
collection DOAJ
description <h4>Background</h4>To achieve sustainable and integrated control of schistosomiasis, it necessitates the implementation of comprehensive strategies, where effective vaccines could play a pivotal role. The limited identification and validation of schistosome antigens hinders the progress of vaccine development for the disease. Schistosome cysteine proteinases are considered as important targets for novel anti-schistosomiasis immunoprophylaxis due to their primary role in nutrient absorption. Previous research on the Schistosoma japonicum degradome has identified a group of cathepsin L-like proteases (SjCLs) that are up-regulated in hepatic schistosomula and adult worms.<h4>Methods/findings</h4>In this study, five recombinant proteins representing the mature form of these SjCLs, designated as rSjCL1-5, were successfully produced. Mice immunized with the rSjCLs were subsequently challenged with cercariae to evaluate the immunoprotective efficacy of these proteins. The expression and localization of SjCL1 were analyzed by qRT-PCR, western blotting and immunofluorescence assays. Among these five rSjCLs, only the immunization with rSjCL1 conferred partial protection to the mice against S. japonicum infection, resulting in a reduction in worm burden by 34.9% ~ 38.0% and a decrease of egg burden by 46.2% ~ 48.3%. This immunization also effectively mitigated body weight loss and hepatomegaly in the challenged mice. SjCL1 was primarily localized along the intestinal intima of hepatic schistosomula, as well as male and female adults, and on the tegument of male adults. The mature form of SjCL1 was detected in the excretory/secretory products of the parasites. Hepatic schistosomulum treated with SjCL1 antibodies in vitro showed significant growth retardation, although remained viable and developed intestinal heme pigmentation, indicative of hemoglobin digestion.<h4>Conclusions/significance</h4>Our study revealed that SjCL1 is essential for normal parasite growth and shed new light for the development of schistosomiasis vaccines targeting cathepsins, which play a key role in the early intra-mammalian stages of schistosomes.
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spelling doaj-art-d65551485f974cf49801e19d73ee3aea2025-08-20T02:38:51ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352025-07-01197e001324110.1371/journal.pntd.0013241Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.Xianyu PiaoYuanlong WangNing JiangPengfei CaiJiamei DuanShuai LiuQijun ChenNan Hou<h4>Background</h4>To achieve sustainable and integrated control of schistosomiasis, it necessitates the implementation of comprehensive strategies, where effective vaccines could play a pivotal role. The limited identification and validation of schistosome antigens hinders the progress of vaccine development for the disease. Schistosome cysteine proteinases are considered as important targets for novel anti-schistosomiasis immunoprophylaxis due to their primary role in nutrient absorption. Previous research on the Schistosoma japonicum degradome has identified a group of cathepsin L-like proteases (SjCLs) that are up-regulated in hepatic schistosomula and adult worms.<h4>Methods/findings</h4>In this study, five recombinant proteins representing the mature form of these SjCLs, designated as rSjCL1-5, were successfully produced. Mice immunized with the rSjCLs were subsequently challenged with cercariae to evaluate the immunoprotective efficacy of these proteins. The expression and localization of SjCL1 were analyzed by qRT-PCR, western blotting and immunofluorescence assays. Among these five rSjCLs, only the immunization with rSjCL1 conferred partial protection to the mice against S. japonicum infection, resulting in a reduction in worm burden by 34.9% ~ 38.0% and a decrease of egg burden by 46.2% ~ 48.3%. This immunization also effectively mitigated body weight loss and hepatomegaly in the challenged mice. SjCL1 was primarily localized along the intestinal intima of hepatic schistosomula, as well as male and female adults, and on the tegument of male adults. The mature form of SjCL1 was detected in the excretory/secretory products of the parasites. Hepatic schistosomulum treated with SjCL1 antibodies in vitro showed significant growth retardation, although remained viable and developed intestinal heme pigmentation, indicative of hemoglobin digestion.<h4>Conclusions/significance</h4>Our study revealed that SjCL1 is essential for normal parasite growth and shed new light for the development of schistosomiasis vaccines targeting cathepsins, which play a key role in the early intra-mammalian stages of schistosomes.https://doi.org/10.1371/journal.pntd.0013241
spellingShingle Xianyu Piao
Yuanlong Wang
Ning Jiang
Pengfei Cai
Jiamei Duan
Shuai Liu
Qijun Chen
Nan Hou
Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
PLoS Neglected Tropical Diseases
title Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
title_full Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
title_fullStr Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
title_full_unstemmed Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
title_short Schistosoma japonicum cathepsin L1: A potential target for anti-schistosomiasis strategies.
title_sort schistosoma japonicum cathepsin l1 a potential target for anti schistosomiasis strategies
url https://doi.org/10.1371/journal.pntd.0013241
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