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Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection

IFN-stimulated gene (ISG) 15 is a ubiquitin-like protein induced after type I IFN stimulation. There is a dearth of in vivo models to study free unconjugated ISG15 function. We found that free ISG15 enhances the production of IFN-γ and IL-1β during murine infection with Toxoplasma gondii. In our mod...

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Autores principales: Napolitano, Anna, van der Veen, Annemarthe G., Bunyan, Monique, Borg, Annabel, Frith, David, Howell, Steven, Kjaer, Svend, Beling, Antje, Snijders, Ambrosius P., Knobeloch, Klaus-Peter, Frickel, Eva-Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036233/
https://www.ncbi.nlm.nih.gov/pubmed/29891555
http://dx.doi.org/10.4049/jimmunol.1701322
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author Napolitano, Anna
van der Veen, Annemarthe G.
Bunyan, Monique
Borg, Annabel
Frith, David
Howell, Steven
Kjaer, Svend
Beling, Antje
Snijders, Ambrosius P.
Knobeloch, Klaus-Peter
Frickel, Eva-Maria
author_facet Napolitano, Anna
van der Veen, Annemarthe G.
Bunyan, Monique
Borg, Annabel
Frith, David
Howell, Steven
Kjaer, Svend
Beling, Antje
Snijders, Ambrosius P.
Knobeloch, Klaus-Peter
Frickel, Eva-Maria
author_sort Napolitano, Anna
collection PubMed
description IFN-stimulated gene (ISG) 15 is a ubiquitin-like protein induced after type I IFN stimulation. There is a dearth of in vivo models to study free unconjugated ISG15 function. We found that free ISG15 enhances the production of IFN-γ and IL-1β during murine infection with Toxoplasma gondii. In our model, ISG15 is induced in a type I IFN–dependent fashion and released into the serum. Increased ISG15 levels are dependent on an actively invading and replicating parasite. Two cysteine residues in the hinge domain are necessary determinants for ISG15 to induce increased cytokine levels during infection. Increased ISG15 is concurrent with an influx of IL-1β–producing CD8α(+) dendritic cells to the site of infection. In this article, we present Toxoplasma infection as a novel in vivo murine model to study the immunomodulatory properties of free ISG15 and uniquely link it to IL-1β production by CD8α(+) dendritic cells driven by two cysteines in the hinge region of the protein.
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spelling pubmed-60362332018-07-10 Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection Napolitano, Anna van der Veen, Annemarthe G. Bunyan, Monique Borg, Annabel Frith, David Howell, Steven Kjaer, Svend Beling, Antje Snijders, Ambrosius P. Knobeloch, Klaus-Peter Frickel, Eva-Maria J Immunol Infectious Disease and Host Response IFN-stimulated gene (ISG) 15 is a ubiquitin-like protein induced after type I IFN stimulation. There is a dearth of in vivo models to study free unconjugated ISG15 function. We found that free ISG15 enhances the production of IFN-γ and IL-1β during murine infection with Toxoplasma gondii. In our model, ISG15 is induced in a type I IFN–dependent fashion and released into the serum. Increased ISG15 levels are dependent on an actively invading and replicating parasite. Two cysteine residues in the hinge domain are necessary determinants for ISG15 to induce increased cytokine levels during infection. Increased ISG15 is concurrent with an influx of IL-1β–producing CD8α(+) dendritic cells to the site of infection. In this article, we present Toxoplasma infection as a novel in vivo murine model to study the immunomodulatory properties of free ISG15 and uniquely link it to IL-1β production by CD8α(+) dendritic cells driven by two cysteines in the hinge region of the protein. AAI 2018-07-15 2018-06-11 /pmc/articles/PMC6036233/ /pubmed/29891555 http://dx.doi.org/10.4049/jimmunol.1701322 Text en Copyright © 2018 The Authors https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the CC BY 4.0 Unported license.
spellingShingle Infectious Disease and Host Response
Napolitano, Anna
van der Veen, Annemarthe G.
Bunyan, Monique
Borg, Annabel
Frith, David
Howell, Steven
Kjaer, Svend
Beling, Antje
Snijders, Ambrosius P.
Knobeloch, Klaus-Peter
Frickel, Eva-Maria
Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title_full Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title_fullStr Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title_full_unstemmed Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title_short Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α(+) Dendritic Cells at the Site of Infection
title_sort cysteine-reactive free isg15 generates il-1β–producing cd8α(+) dendritic cells at the site of infection
topic Infectious Disease and Host Response
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036233/
https://www.ncbi.nlm.nih.gov/pubmed/29891555
http://dx.doi.org/10.4049/jimmunol.1701322
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