2. Academic Validation
  3. Fc gamma receptor IIa suppresses type I and III interferon production by human myeloid immune cells

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

  • Eur J Immunol. 2018 Nov;48(11):1796-1809. doi: 10.1002/eji.201847615.
Melissa Newling 1 2,  Willianne Hoepel 1 2,  Lisa T C Vogelpoel 2,  Marieke H Heineke 3,  Johan A van Burgsteden 1 2,  Esther W M Taanman-Kueter 2,  Dirk Eggink 4,  Taco W Kuijpers 5 6,  Tim Beaumont 7,  Marjolein van Egmond 3 8,  Martien L Kapsenberg 2,  Dominique L P Baeten 1 2,  Jeroen den Dunnen 1 2,  Esther C de Jong 2
Affiliations

Affiliations

  • 1 Amsterdam Rheumatology and Immunology Center, location Academic Medical Center (AMC), Amsterdam, The Netherlands.
  • 2 Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam, The Netherlands.
  • 3 Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, The Netherlands.
  • 4 Amsterdam UMC, University of Amsterdam, Department of Medical Microbiology, Amsterdam, The Netherlands.
  • 5 Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
  • 6 Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
  • 7 AIMM Therapeutics, AMC, Amsterdam, The Netherlands.
  • 8 Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
PMID: 30184252 DOI: 10.1002/eji.201847615
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.

Keywords

Fc gamma receptor; IgG; antigen-presenting cell; human myeloid immune cells; type I interferon.

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