Journal article
FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response
The Journal of immunology (1950), Vol.194(9), pp.4240-4250
05/01/2015
DOI: 10.4049/jimmunol.1401296
PMCID: PMC4820833
PMID: 25821224
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.
Details
- Title: Subtitle
- FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response
- Creators
- Marcella Flores - 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; andClaude Chew - 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; andKevin Tyan - 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; andWu Qing Huang - 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; andAliasger Salem - Division of Pharmaceuticals, College of Pharmacy, University of Iowa, Iowa City, IA 52242Raphael Clynes - 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
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.194(9), pp.4240-4250
- DOI
- 10.4049/jimmunol.1401296
- PMID
- 25821224
- PMCID
- PMC4820833
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 DK070999 / NIDDK NIH HHS S10 RR027050 / NCRR NIH HHS R01 DK70999 / NIDDK NIH HHS R01 CA164309 / NCI NIH HHS 1R01CA164309 / NCI NIH HHS
- Language
- English
- Date published
- 05/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9983985822702771
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