title: FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response.
abstract: The type I IFN (IFN-α) response is crucial for viral clearance during primary viral infections. Plasmacytoid dendritic cells (pDCs) are important early responders during systemic viral infections and, in some cases, are the sole producers of IFN-α. However, their role in IFN-α production during memory responses is unclear. We found that IFN-α production is absent during a murine viral memory response, despite colocalization of virus and pDCs to the splenic marginal zone. The absence of IFN was dependent on circulating Ab and was reversed by the transgenic expression of the activating human FcγRIIA receptor on pDCs. Furthermore, FcγRIIB was required for Sendai virus immune complex uptake by splenic pDCs in vitro, and internalization via FcγRIIb prevented cargo from accessing TLR signaling endosomes. Thus, pDCs bind viral immune complexes via FcγRIIB and prevent IFN-α production in vivo during viral memory responses. This Ab-dependent IFN-α regulation may be an important mechanism by which the potentially deleterious effects of IFN-α are prevented during a secondary infection.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; Department of Medicine, Columbia University Medical Center, New York, NY 10032; Department of Dermatology, Columbia University Medical Center, New York, NY 10032; and.
authors.forename: Marcella
authors.initials: M
authors.lastname: Flores
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; Department of Medicine, Columbia University Medical Center, New York, NY 10032; Department of Dermatology, Columbia University Medical Center, New York, NY 10032; and.
authors.forename: Claude
authors.initials: C
authors.lastname: Chew
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; Department of Medicine, Columbia University Medical Center, New York, NY 10032; Department of Dermatology, Columbia University Medical Center, New York, NY 10032; and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tyan
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; Department of Medicine, Columbia University Medical Center, New York, NY 10032; Department of Dermatology, Columbia University Medical Center, New York, NY 10032; and.
authors.forename: Wu Qing
authors.initials: WQ
authors.lastname: Huang
authors.affiliation: Division of Pharmaceuticals, College of Pharmacy, University of Iowa, Iowa City, IA 52242.
authors.forename: Aliasger
authors.initials: A
authors.lastname: Salem
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; Department of Medicine, Columbia University Medical Center, New York, NY 10032; Department of Dermatology, Columbia University Medical Center, New York, NY 10032; and raphael.clynes@bms.com.
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D021381:Protein Transport; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D029082:Sendai virus / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014777:Virus Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; C499173:FCGR2B protein, human; C080568:Fc gamma receptor IIA; D007370:Interferon Type I; D017452:Receptors, IgG; D051217:Toll-Like Receptor 9
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