title: Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo.
abstract: Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I-mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Swiecki
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wang
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D025461:Feedback, Physiological; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007370:Interferon Type I
references.citation: J Infect Dis. 2004 Dec 1;190(11):1919-26
references.pmid: 15529255
references.citation: J Immunol. 2002 Sep 15;169(6):3006-14
references.pmid: 12218115
references.citation: Cell. 2007 Apr 20;129(2):423-33
references.pmid: 17448999
references.citation: J Infect Dis. 2004 May 1;189(9):1646-55
references.pmid: 15116301
references.citation: Blood. 2004 Feb 15;103(4):1433-7
references.pmid: 14563635
references.citation: Nat Immunol. 2001 Dec;2(12):1144-50
references.pmid: 11713464
references.citation: Blood. 2008 Dec 1;112(12):4598-608
references.pmid: 18787223
references.citation: J Exp Med. 2010 Sep 27;207(10):2053-63
references.pmid: 20837696
references.citation: Immunity. 2010 Dec 14;33(6):955-66
references.pmid: 21130004
references.citation: Science. 1999 Nov 26;286(5445):1735-8
references.pmid: 10576740
references.citation: Nat Rev Immunol. 2008 Aug;8(8):594-606
references.pmid: 18641647
references.citation: Science. 2006 May 12;312(5775):879-82
references.pmid: 16690858
references.citation: J Exp Med. 2000 Jul 17;192(2):219-26
references.pmid: 10899908
references.citation: Cell Host Microbe. 2008 Oct 16;4(4):374-86
references.pmid: 18854241
references.citation: PLoS One. 2011;6(6):e20189
references.pmid: 21674051
references.citation: J Clin Immunol. 2004 Nov;24(6):637-46
references.pmid: 15622448
references.citation: Immunity. 2008 Sep 19;29(3):352-61
references.pmid: 18799143
references.citation: PLoS Pathog. 2009 May;5(5):e1000413
references.pmid: 19424421
references.citation: Blood. 2009 Aug 13;114(7):1344-54
references.pmid: 19531658
references.citation: Nat Rev Immunol. 2011 Mar;11(3):176-86
references.pmid: 21350578
references.citation: Eur J Immunol. 2009 Jul;39(7):1807-18
references.pmid: 19544312
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2993-8
references.pmid: 18287072
references.citation: J Virol. 2004 May;78(10):5223-32
references.pmid: 15113904
references.citation: Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
references.pmid: 18097445
references.citation: J Exp Med. 2009 Jul 6;206(7):1589-602
references.pmid: 19564349
references.citation: Clin Immunol. 2008 Mar;126(3):235-42
references.pmid: 17916442
references.citation: Immunol Rev. 2010 Jul;236:11-27
references.pmid: 20636805
references.citation: J Exp Med. 2005 Apr 4;201(7):1157-67
references.pmid: 15795237
references.citation: J Clin Immunol. 2004 Nov;24(6):647-52
references.pmid: 15622449
references.citation: J Immunol. 2009 Jun 1;182(11):7178-89
references.pmid: 19454715