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

Abstract
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.
AuthorsAnna Napolitano, Annemarthe G van der Veen, Monique Bunyan, Annabel Borg, David Frith, Steven Howell, Svend Kjaer, Antje Beling, Ambrosius P Snijders, Klaus-Peter Knobeloch, Eva-Maria Frickel
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 201 Issue 2 Pg. 604-614 (07 15 2018) ISSN: 1550-6606 [Electronic] United States
PMID29891555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 The Authors.
Chemical References
  • CD8 Antigens
  • CD8alpha antigen
  • Cytokines
  • G1p2 protein, mouse
  • Interferon Type I
  • Interleukin-1beta
  • Ubiquitins
  • Interferon-gamma
  • Cysteine
Topics
  • Animals
  • CD8 Antigens (metabolism)
  • Cell Movement
  • Cells, Cultured
  • Cysteine (genetics)
  • Cytokines (genetics, metabolism)
  • Dendritic Cells (immunology)
  • Disease Models, Animal
  • Immunomodulation
  • Interferon Type I (immunology)
  • Interferon-gamma (metabolism)
  • Interleukin-1beta (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Conformation
  • Toxoplasma (physiology)
  • Toxoplasmosis (immunology)
  • Ubiquitins (genetics, metabolism)

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