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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,
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
RVO 60077344
Parazitologická ústav, Akademie Věd České Republiky
RVO 61388963
Ústav Organické Chemie a Biochemie, Akademie Věd České Republiky
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
- MeSH
- cystatiny klasifikace genetika farmakologie MeSH
- cytokiny metabolismus MeSH
- epoxidové sloučeniny metabolismus MeSH
- fylogeneze MeSH
- imunosupresiva chemie metabolismus farmakologie MeSH
- klíště chemie genetika metabolismus MeSH
- krystalografie rentgenová MeSH
- makrofágy účinky léků metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- proteiny členovců chemie genetika farmakologie MeSH
- proteolýza účinky léků MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie aminokyselin MeSH
- slinné cystatiny chemie genetika farmakologie MeSH
- T-lymfocyty účinky léků metabolismus MeSH
- tyrosin analogy a deriváty metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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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