<i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin

Alveolar Echinococcosis (AE) is a serious zoonotic disease caused by infection of <i>Echinococcus multilocularis</i> larvae. To survive within the host, <i>E. multilocularis</i> has developed a complex immune evasion mechanism including the inhibition of complement activation...

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Main Authors: Yuxiao Shao, Meng Xia, Yinghui Song, Yan Yan, Xiaofang Dong, Haoran Zong, Bin Zhan, Yanhai Wang, Limei Zhao
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/4/354
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author Yuxiao Shao
Meng Xia
Yinghui Song
Yan Yan
Xiaofang Dong
Haoran Zong
Bin Zhan
Yanhai Wang
Limei Zhao
author_facet Yuxiao Shao
Meng Xia
Yinghui Song
Yan Yan
Xiaofang Dong
Haoran Zong
Bin Zhan
Yanhai Wang
Limei Zhao
author_sort Yuxiao Shao
collection DOAJ
description Alveolar Echinococcosis (AE) is a serious zoonotic disease caused by infection of <i>Echinococcus multilocularis</i> larvae. To survive within the host, <i>E. multilocularis</i> has developed a complex immune evasion mechanism including the inhibition of complement activation. This study focused on a calreticulin secreted by <i>E. multilocularis</i> (<i>Em</i>CRT) and its role in binding ability to human MBL and inhibiting MBL-mannose-mediated lectin pathway of complement activation. Results demonstrated the binding of recombinant <i>Em</i>CRT protein to both external and natural MBL in serum and the subsequent inhibition of MBL-mannose-initiated lectin pathway reflected by the reduced formation of complement intermediate products C3b and C4b. Fragment mapping determined that the MBL binding site was located within the S-domain of <i>Em</i>CRT. Combining with its role in inhibiting C1q-initiated classical complement activation in our previous study, the inhibition of MBL-mannose-initiated lectin pathway identified in this study suggests <i>Em</i>CRT plays an important role in the immune evasion of <i>E. multilocularis</i> alveolar larvae against host complement attack as a survival strategy within human tissue. This study supports the approach of using <i>Em</i>CRT as a good candidate for vaccine and drug development against <i>E. multilocularis</i> infection.
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spelling doaj-art-ec6cf9a4ff994b00ab9cc1ec7e0c19eb2025-08-20T02:28:38ZengMDPI AGPathogens2076-08172025-04-0114435410.3390/pathogens14040354<i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding LectinYuxiao Shao0Meng Xia1Yinghui Song2Yan Yan3Xiaofang Dong4Haoran Zong5Bin Zhan6Yanhai Wang7Limei Zhao8Department of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaDepartment of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USAParasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen 361102, ChinaDepartment of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, ChinaAlveolar Echinococcosis (AE) is a serious zoonotic disease caused by infection of <i>Echinococcus multilocularis</i> larvae. To survive within the host, <i>E. multilocularis</i> has developed a complex immune evasion mechanism including the inhibition of complement activation. This study focused on a calreticulin secreted by <i>E. multilocularis</i> (<i>Em</i>CRT) and its role in binding ability to human MBL and inhibiting MBL-mannose-mediated lectin pathway of complement activation. Results demonstrated the binding of recombinant <i>Em</i>CRT protein to both external and natural MBL in serum and the subsequent inhibition of MBL-mannose-initiated lectin pathway reflected by the reduced formation of complement intermediate products C3b and C4b. Fragment mapping determined that the MBL binding site was located within the S-domain of <i>Em</i>CRT. Combining with its role in inhibiting C1q-initiated classical complement activation in our previous study, the inhibition of MBL-mannose-initiated lectin pathway identified in this study suggests <i>Em</i>CRT plays an important role in the immune evasion of <i>E. multilocularis</i> alveolar larvae against host complement attack as a survival strategy within human tissue. This study supports the approach of using <i>Em</i>CRT as a good candidate for vaccine and drug development against <i>E. multilocularis</i> infection.https://www.mdpi.com/2076-0817/14/4/354<i>Echinococcus multilocularis</i>calreticulincomplement lectin activationmannose-binding lectinimmune evasion
spellingShingle Yuxiao Shao
Meng Xia
Yinghui Song
Yan Yan
Xiaofang Dong
Haoran Zong
Bin Zhan
Yanhai Wang
Limei Zhao
<i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
Pathogens
<i>Echinococcus multilocularis</i>
calreticulin
complement lectin activation
mannose-binding lectin
immune evasion
title <i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
title_full <i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
title_fullStr <i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
title_full_unstemmed <i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
title_short <i>Echinococcus multilocularis</i> Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
title_sort i echinococcus multilocularis i calreticulin inhibits lectin pathway of complement activation by directly binding to mannose binding lectin
topic <i>Echinococcus multilocularis</i>
calreticulin
complement lectin activation
mannose-binding lectin
immune evasion
url https://www.mdpi.com/2076-0817/14/4/354
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