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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F19%3A43899427" target="_blank" >RIV/60076658:12310/19:43899427 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60077344:_____/19:00519639 RIV/61388963:_____/19:00519639

Výsledek na webu

<a href="https://link.springer.com/content/pdf/10.1007%2Fs00018-019-03034-3.pdf" target="_blank" >https://link.springer.com/content/pdf/10.1007%2Fs00018-019-03034-3.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00018-019-03034-3" target="_blank" >10.1007/s00018-019-03034-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cellular and Molecular Life Science

ISSN

1420-682X

e-ISSN

—

Svazek periodika

76

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

11

Strana od-do

2003-2013

Kód UT WoS článku

000465438900011

EID výsledku v databázi Scopus

2-s2.0-85061431964