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

0519639 - BC 2020 RIV CH eng J - Journal Article
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
R&D Projects: GA ČR(CZ) GA19-07247S; GA MŠMT(CZ) EF16_019/0000729; GA MŠMT(CZ) EF16_019/0000759
Institutional support: RVO:60077344 ; RVO:61388963
Keywords : cd4(+) t-cells * sialostatin-l * nitric-oxide * schistosoma-japonicum * ixodes-scapularis * protein * inhibitor * responses * expression * mosquito * Cathepsin * Crystal structure * Immune responses * Ixodes ricinus * Saliva
OECD category: Biochemistry and molecular biology; Biochemistry and molecular biology (UOCHB-X)
Impact factor: 6.496, year: 2019
Method of publishing: Limited access
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.
Permanent Link: http://hdl.handle.net/11104/0304643