Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro

0554108 - BC 2022 RIV CH eng J - Článek v odborném periodiku
Chlastáková, A. - Kotál, Jan - Beránková, Z. - Kaščáková, B. - Martins, Larissa Almeida - Langhansová, H. - Prudníková, T. - Ederova, M. - Kutá Smatanová, I. - Kotsyfakis, Michalis - Chmelař, J.
Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro.
Frontiers in Immunology. Roč. 12, MAR 1 2021 (2021), č. článku 626200. ISSN 1664-3224. E-ISSN 1664-3224
Grant CEP: GA ČR(CZ) GA19-07247S
Institucionální podpora: RVO:60077344
Klíčová slova: 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
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 8.787, rok: 2021
Způsob publikování: Open access
https://www.frontiersin.org/articles/10.3389/fimmu.2021.626200/full

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.
Trvalý link: http://hdl.handle.net/11104/0328746