TY - JOUR
T1 - Cysteine-reactive free ISG15 generates IL-1b–Producing CD8a+ dendritic cells at the site of infection
AU - Napolitano, Anna
AU - Van Der Veen, Annemarthe G.
AU - Bunyan, Monique
AU - Borg, Annabel
AU - Frith, David
AU - Howell, Steven
AU - Kjaer, Svend
AU - Beling, Antje
AU - Snijders, Ambrosius P.
AU - Knobeloch, Klaus Peter
AU - Frickel, Eva Maria
PY - 2018/7/15
Y1 - 2018/7/15
N2 - 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-g and IL-1b 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-1b–producing CD8a+ 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-1b production by CD8a+ dendritic cells driven by two cysteines in the hinge region of the protein.
AB - 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-g and IL-1b 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-1b–producing CD8a+ 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-1b production by CD8a+ dendritic cells driven by two cysteines in the hinge region of the protein.
UR - http://www.scopus.com/inward/record.url?scp=85049828806&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701322
DO - 10.4049/jimmunol.1701322
M3 - Article
SN - 0022-1767
VL - 201
SP - 604
EP - 614
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -