Fc gamma receptor IIa suppresses type I and III interferon production by human myeloid immune cells

Type I and type III interferons (IFNs) are fundamental for antiviral immunity, but prolonged expression is also detrimental to the host. Therefore, upon viral infection high levels of type I and III IFNs are followed by a strong and rapid decline. However, the mechanisms responsible for this suppres...

Full description

Saved in:
Bibliographic Details
Published in:European journal of immunology 2018-11, Vol.48 (11), p.1796-1809
Main Authors: Newling, Melissa, Hoepel, Willianne, Vogelpoel, Lisa T.C., Heineke, Marieke H., Burgsteden, Johan A., Taanman‐Kueter, Esther W.M., Eggink, Dirk, Kuijpers, Taco W., Beaumont, Tim, Egmond, Marjolein, Kapsenberg, Martien L., Baeten, Dominique L.P., Dunnen, Jeroen, Jong, Esther C. de
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Antigen-presenting cells
antigen‐presenting cell
Basic
Fc gamma receptor
Fc receptors
human myeloid immune cells
IgG
Immunoglobulin G
Infections
Influenza
Innate immunity
Interferon
Myeloid cells
Negative feedback
Opsonization
Respiratory syncytial virus
Syk protein
Transcription
type I interferon
Viral infections
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Type I and type III interferons (IFNs) are fundamental for antiviral immunity, but prolonged expression is also detrimental to the host. Therefore, upon viral infection high levels of type I and III IFNs are followed by a strong and rapid decline. However, the mechanisms responsible for this suppression are still largely unknown. Here, we show that IgG opsonization of model viruses influenza and respiratory syncytial virus (RSV) strongly and selectively suppressed type I and III IFN production by various human antigen‐presenting cells. This suppression was induced by selective inhibition of TLR, RIG‐I‐like receptor, and STING‐dependent type I and III IFN gene transcription. Surprisingly, type I and III IFN suppression was mediated by Syk and PI3K independent inhibitory signaling via FcγRIIa, thereby identifying a novel non‐canonical FcγRIIa pathway in myeloid cells. Together, these results indicate that IgG opsonization of viruses functions as a novel negative feedback mechanism in humans, which may play a role in the selective suppression of type I and III IFN responses during the late‐phase of viral infections. In addition, activation of this pathway may be used as a tool to limit type I IFN‐associated pathology. In early‐phase viral infections, high levels of type I and III IFNs are produced. During late‐phase viral infections, virus opsonization results in IgG immune complexes, which suppresses type I and III IFN responses via FcyRIIa. This prevents damage to the host, and allows for increased B and T cell responses.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201847615