The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin

0519639 - BC 2020 RIV CH eng J - Článek v odborném periodiku
Kotál, Jan - Stergiou, N. - Buša, Michal - Chlastáková, A. - Beránková, Z. - Řezáčová, Pavlína - Langhansová, H. - Schwarz, Alexandra - Calvo, E. - Kopecký, J. - Mareš, Michael - Schmitt, E. - Chmelař, J. - Kotsyfakis, Michalis
The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin.
Cellular and Molecular Life Sciences. Roč. 76, č. 10 (2019), s. 2003-2013. ISSN 1420-682X. E-ISSN 1420-9071
Grant CEP: GA ČR(CZ) GA19-07247S; GA MŠMT(CZ) EF16_019/0000729; GA MŠMT(CZ) EF16_019/0000759
Institucionální podpora: RVO:60077344 ; RVO:61388963
Klíčová slova: cd4(+) t-cells * sialostatin-l * nitric-oxide * schistosoma-japonicum * ixodes-scapularis * protein * inhibitor * responses * expression * mosquito * Cathepsin * Crystal structure * Immune responses * Ixodes ricinus * Saliva
Obor OECD: Biochemistry and molecular biology; Biochemistry and molecular biology (UOCHB-X)
Impakt faktor: 6.496, rok: 2019
Způsob publikování: Omezený přístup
https://link.springer.com/article/10.1007%2Fs00018-019-03034-3

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 angstrom resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN- 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.
Trvalý link: http://hdl.handle.net/11104/0304643