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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAI
2018
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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. |
format | Online Article Text |
id | pubmed-6036233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | AAI |
record_format | MEDLINE/PubMed |
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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