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

Melissa Newling, Willianne Hoepel, Lisa T C Vogelpoel, Marieke H Heineke, Johan A van Burgsteden, Esther W M Taanman-Kueter, Dirk Eggink, Taco W Kuijpers, Tim Beaumont, Marjolein van Egmond, Martien L Kapsenberg, Dominique L P Baeten, Jeroen den Dunnen, Esther C de Jong

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1796-1809
Number of pages14
JournalEuropean Journal of Immunology
Volume48
Issue number11
DOIs
Publication statusPublished - Nov 2018

Cite this

Newling, M., Hoepel, W., Vogelpoel, L. T. C., Heineke, M. H., van Burgsteden, J. A., Taanman-Kueter, E. W. M., ... Jong, E. C. D. (2018). Fc gamma receptor IIa suppresses type I and III interferon production by human myeloid immune cells. European Journal of Immunology, 48(11), 1796-1809. https://doi.org/10.1002/eji.201847615