The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin
| Autor: | Edgar Schmitt, Natascha Stergiou, Helena Langhansová, Eric Calvo, Michail Kotsyfakis, Alexandra Schwarz, Jan Kotál, Michael Mareš, Zuzana Beránková, Jan Kopecký, Pavlína Řezáčová, Adéla Chlastáková, Jindřich Chmelař, Michal Buša |
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| Rok vydání: | 2019 |
| Předmět: |
Saliva
T-Lymphocytes Biology Crystallography X-Ray Nitric Oxide Arthropod Proteins law.invention Cellular and Molecular Neuroscience Immune system In vivo law Animals Amino Acid Sequence Molecular Biology Phylogeny Pharmacology Cathepsin Ixodes Sequence Homology Amino Acid Macrophages Cell Biology Cystatins Cysteine protease In vitro Cell biology Proteolysis Recombinant DNA Cytokines Epoxy Compounds Salivary Cystatins Tyrosine Molecular Medicine Female Cystatin Immunosuppressive Agents |
| Zdroj: | Cellular and Molecular Life Sciences. 76:2003-2013 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | To successfully feed, ticks inject pharmacoactive molecules into the vertebrate host including cystatin cysteine protease inhibitors. However, the molecular and cellular events modulated by tick saliva remain largely unknown. Here, we describe and characterize a novel immunomodulatory cystatin, Iristatin, which is upregulated in the salivary glands of feeding Ixodes ricinus ticks. We present the crystal structure of Iristatin at 1.76 A resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN-γ production by different T-cell populations, IL-6 and IL-9 production by mast cells, and nitric oxide production by macrophages. Furthermore, Iristatin inhibited OVA antigen-induced CD4+ T-cell proliferation and leukocyte recruitment in vivo and in vitro. Our results indicate that Iristatin affects wide range of anti-tick immune responses in the vertebrate host and may be exploitable as an immunotherapeutic. |
| Databáze: | OpenAIRE |
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