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

J. Kotál, N. Stergiou, M. Buša, A. Chlastáková, Z. Beránková, P. Řezáčová, H. Langhansová, A. Schwarz, E. Calvo, J. Kopecký, M. Mareš, E. Schmitt, J. Chmelař, M. Kotsyfakis,

. 2019 ; 76 (10) : 2003-2013. [pub] 20190212

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19027822

Grantová podpora
RVO 60077344 Parazitologická ústav, Akademie Věd České Republiky
RVO 61388963 Ústav Organické Chemie a Biochemie, Akademie Věd České Republiky

E-zdroje Online Plný text

NLK PubMed Central od 1997
ProQuest Central od 1997-01-01 do Před 1 rokem
Medline Complete (EBSCOhost) od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 1997-01-01 do Před 1 rokem

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 Å 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.

Citace poskytuje Crossref.org

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