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Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro
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SYSNO ASEP 0554108 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro Author(s) Chlastáková, A. (CZ)
Kotál, Jan (BC-A) RID, ORCID
Beránková, Z. (CZ)
Kaščáková, B. (CZ)
Martins, Larissa Almeida (BC-A) RID, ORCID
Langhansová, H. (CZ)
Prudníková, T. (CZ)
Ederova, M. (CZ)
Kutá Smatanová, I. (CZ)
Kotsyfakis, Michalis (BC-A) RID, ORCID
Chmelař, J. (CZ)Number of authors 11 Article number 626200 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 12, MAR 1 2021 (2021)Number of pages 20 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords antithrombin-iii ; factor-viia ; inhibitors ; serpins ; infestations ; family ; glycosylation ; annotation ; expression ; interface ; tick ; serpin ; X-ray crystallography ; blood coagulation ; inflammation ; adaptive immunity ; Ixodes ricinus ; saliva Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA19-07247S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 000628780000001 EID SCOPUS 85102710767 DOI 10.3389/fimmu.2021.626200 Annotation Tick saliva is a rich source of pharmacologically and immunologically active molecules. These salivary components are indispensable for successful blood feeding on vertebrate hosts and are believed to facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-3, a protein expressed in the salivary glands of the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Belonging to the serpin superfamily of protease inhibitors, Iripin-3 strongly inhibited the proteolytic activity of serine proteases kallikrein and matriptase. In an in vitro setup, Iripin-3 was capable of modulating the adaptive immune response as evidenced by reduced survival of mouse splenocytes, impaired proliferation of CD4(+) T lymphocytes, suppression of the T helper type 1 immune response, and induction of regulatory T cell differentiation. Apart from altering acquired immunity, Iripin-3 also inhibited the extrinsic blood coagulation pathway and reduced the production of pro-inflammatory cytokine interleukin-6 by lipopolysaccharide-stimulated bone marrow-derived macrophages. In addition to its functional characterization, we present the crystal structure of cleaved Iripin-3 at 1.95 angstrom resolution. Iripin-3 proved to be a pluripotent salivary serpin with immunomodulatory and anti-hemostatic properties that could facilitate tick feeding via the suppression of host anti-tick defenses. Physiological relevance of Iripin-3 activities observed in vitro needs to be supported by appropriate in vivo experiments. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2022 Electronic address https://www.frontiersin.org/articles/10.3389/fimmu.2021.626200/full
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