Parasites, Hosts and Diseases

"cystatin"

Original Articles

Identification of the protease inhibitory domain of Trichinella spiralis novel cystatin (TsCstN): Thassanee Yuthithum, Orawan Phuphisut, Onrapak Reamtong, Nathamon Kosoltanapiwat, Salisa Chaimon, Porntida Kobpornchai, Charin Thawornkuno, Preeyarat Malaithong, Orathai Sawatdichaikul, Poom Adisakwattana; Parasites Hosts Dis 2024;62(3):330-341.
Published online August 26, 2024; DOI: https://doi.org/10.3347/PHD.24026

The Trichinella spiralis novel cystatin (TsCstN) inhibits cathepsin L (CatL) activity and inflammation of macrophages during lipopolysaccharide (LPS) induction. To identify the protease inhibitory region, this study applied an in silico modeling approach to simulate truncation sites of TsCstN (Ts01), which created four truncated forms, including TsCstN^∆1-39 (Ts02), TsCstN^∆1-71 (Ts03), TsCstN^{∆1-20, ∆73-117} (Ts04), and TsCstN^{∆1-20, ∆42-117} (Ts05). The superimposition of these truncates modeled with AlphaFold Colab indicated that their structures were more akin to Ts01 than those modeled with I-TASSER. Moreover, Ts04 exhibited the closest resemblance to the structure of Ts01. The recombinant Ts01 (rTs01) and truncated proteins (rTs02, rTs03, and rTs04) were successfully expressed in a prokaryotic expression system while Ts05 was synthesized, with sizes of approximately 14, 12, 8, 10, and 2.5 kDa, respectively. When determining the inhibition of CatL activity, both rTs01 and rTs04 effectively reduced CatL activity in vitro. Thus, the combination of the α1 and L1 regions may be sufficient to inhibit CatL. This study provides comprehensive insights into TsCstN, particularly regarding its protein function and inhibitory domains against CatL.

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Systems biology of Haemonchus contortus – Advancing biotechnology for parasitic nematode control
Yuanting Zheng, Neil D. Young, Tao Wang, Bill C.H. Chang, Jiangning Song, Robin B. Gasser
Biotechnology Advances.2025; 81: 108567. CrossRef
Therapeutic potentials of Trichinella spiralis in immune disorders: From allergy to autoimmunity
Minkyoung Cho, Hak Sun Yu
Parasites, Hosts and Diseases.2025; 63(2): 123. CrossRef

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71 Download
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Molecular Characteristics and Potent Immunomodulatory Activity of Fasciola hepatica Cystatin: Kai Zhang, Yucheng Liu, Guowu Zhang, Xifeng Wang, Zhiyuan Li, Yunxia Shang, Chengcheng Ning, Chunhui Ji, Xuepeng Cai, Xianzhu Xia, Jun Qiao, Qingling Meng; Korean J Parasitol 2022;60(2):117-126.
Published online April 20, 2022; DOI: https://doi.org/10.3347/kjp.2022.60.2.117

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

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Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells
Nathalie Acevedo, Ana Lozano, Josefina Zakzuk, Kevin Llinás-Caballero, David Brodin, Peter Nejsum, Andrew R. Williams, Luis Caraballo
Frontiers in Immunology.2024;[Epub] CrossRef
Helminth-derived molecules: Pathogenic and pharmacopeial roles
Yu Zhang, Chunxiang Shen, Xinyi Zhu, Chiuan Yee Leow, Minjun Ji, Zhipeng Xu
The Journal of Biomedical Research.2024; 38(6): 547. CrossRef
An evolutionary molecular adaptation of an unusual stefin from the liver fluke Fasciola hepatica redefines the cystatin superfamily
Michal Buša, Zuzana Matoušková, Pavla Bartošová-Sojková, Petr Pachl, Pavlína Řezáčová, Ramon Marc Eichenberger, Peter Deplazes, Martin Horn, Saša Štefanić, Michael Mareš
Journal of Biological Chemistry.2023; 299(3): 102970. CrossRef
Type I Cystatin Derived from Fasciola gigantica Suppresses Macrophage-Mediated Inflammatory Responses
Pathanin Chantree, Mayuri Tarasuk, Parisa Prathaphan, Jittiporn Ruangtong, Mantana Jamklang, Sirilak Chumkiew, Pongsakorn Martviset
Pathogens.2023; 12(3): 395. CrossRef
Cystatins from the Human Liver Fluke Opisthorchis viverrini: Molecular Characterization and Functional Analysis
Amornrat Geadkaew-Krenc, Rudi Grams, Sinee Siricoon, Nanthawat Kosa, Dawid Krenc, Wansika Phadungsil, Pongsakorn Martviset
Pathogens.2023; 12(7): 949. CrossRef
Antigens from the Helminth Fasciola hepatica Exert Antiviral Effects against SARS-CoV-2 In Vitro
Judit Serrat, Clara Francés-Gómez, David Becerro-Recio, Javier González-Miguel, Ron Geller, Mar Siles-Lucas
International Journal of Molecular Sciences.2023; 24(14): 11597. CrossRef
Cysticercus pisiformis-derived novel-miR1 targets TLR2 to inhibit the immune response in rabbits
Guoliang Chen, Guiting Pu, Liqun Wang, Yanping Li, Tingli Liu, Hong Li, Shaohua Zhang, Xuelin Wang, Xiaolei Liu, Xuenong Luo
Frontiers in Immunology.2023;[Epub] CrossRef
Fasciolosis: pathogenesis, host-parasite interactions, and implication in vaccine development
Luis Miguel Flores-Velázquez, María Teresa Ruiz-Campillo, Guillem Herrera-Torres, Álvaro Martínez-Moreno, Francisco Javier Martínez-Moreno, Rafael Zafra, Leandro Buffoni, Pablo José Rufino-Moya, Verónica Molina-Hernández, José Pérez
Frontiers in Veterinary Science.2023;[Epub] CrossRef

5,490 View
205 Download
9 Web of Science
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Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-10⁺F4/80⁺ Macrophage Recruitment: Sung Won Jang, Min Kyoung Cho, Mi Kyung Park, Shin Ae Kang, Byoung-Kuk Na, Soon Cheol Ahn, Dong-Hee Kim, Hak Sun Yu; Korean J Parasitol 2011;49(3):245-254.
Published online September 30, 2011; DOI: https://doi.org/10.3347/kjp.2011.49.3.245

Abstract
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Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-γ and TNF-α in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-α in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10⁺F4/80⁺ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.

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