title: Multiple effects of dendritic cell depletion on murine norovirus infection.
abstract: Dendritic cells (DCs) are permissive to murine norovirus (MNV) infection in vitro and in vivo. However, their roles during infection in vivo are not well defined. To determine the role of DCs during infection, conventional DCs were depleted from CD11c-DTR mice and infected with a persistent MNV strain. Viral titres in the intestine and secondary lymphoid organs were determined at early time points during infection, and anti-MNV antibody responses were analysed later during infection. Depletion of conventional DCs resulted in increased viral loads in intestinal tissues, impaired generation of antibody responses, and a failure of MNV to efficiently infect lymphoid tissues. These data suggest that DCs play multiple roles in MNV pathogenesis, in both innate immunity and the efficient generation of adaptive immune responses against MNV, as well as by promoting the dissemination of MNV to secondary lymphoid tissues. This is the first study to probe the roles of DCs in controlling and/or facilitating a norovirus infection in vivo and provides the basis for further studies aimed at defining mechanisms by which DCs control MNV replication and promote viral dissemination.
authors: Department of Biomedical and Diagnostic Sciences, University of Detroit Mercy School of Dentistry, Detroit, Michigan 48208, USA.|Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Michael D
authors: MD
authors: Elftman
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Mariam B
authors: MB
authors: Gonzalez-Hernandez
authors: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Nobuhiko
authors: N
authors: Kamada
authors: Molecular Diagnostics Research, Animal Diagnostic Services, Charles River Laboratories, Wilmington, Massachusetts 01887, USA.
authors: Cheryl
authors: C
authors: Perkins
authors: Molecular Diagnostics Research, Animal Diagnostic Services, Charles River Laboratories, Wilmington, Massachusetts 01887, USA.
authors: Kenneth S
authors: KS
authors: Henderson
authors: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Gabriel
authors: G
authors: Núñez
authors: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors: Christiane E
authors: CE
authors: Wobus
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D017250:Caliciviridae Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D007422:Intestines / Q000821:virology; D047589:Leukocyte Reduction Procedures; D008221:Lymphoid Tissue / Q000821:virology; D051379:Mice; D029322:Norovirus / Q000276:immunology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral
references: J Immunol. 2007 Mar 15;178(6):3505-10
references: 17339445
references: Curr Opin Immunol. 2010 Feb;22(1):131-6
references: 20060698
references: Nat Immunol. 2007 Oct;8(10):1086-94
references: 17873879
references: J Immunol. 2003 Nov 15;171(10):5077-84
references: 14607905
references: J Virol. 2007 Oct;81(19):10460-73
references: 17652401
references: Immunity. 2009 Sep 18;31(3):513-25
references: 19733489
references: PLoS Pathog. 2011 Nov;7(11):e1002345
references: 22072965
references: PLoS Pathog. 2009 Feb;5(2):e1000298
references: 19214214
references: Lab Anim. 2009 Apr;43(2):165-73
references: 19015179
references: Cell. 2010 Jun 25;141(7):1135-45
references: 20602997
references: Clin Exp Immunol. 2005 Sep;141(3):398-404
references: 16045728
references: J Exp Med. 2007 Aug 6;204(8):1923-33
references: 17646404
references: Immunity. 2002 Aug;17(2):211-20
references: 12196292
references: J Virol. 2007 Apr;81(7):3251-63
references: 17229692
references: PLoS Biol. 2004 Dec;2(12):e432
references: 15562321
references: J Virol. 2006 Apr;80(8):3985-93
references: 16571815
references: Science. 2005 Jan 14;307(5707):254-8
references: 15653504
references: Science. 2003 Mar 7;299(5612):1575-8
references: 12624267
references: Virol J. 2009 Nov 10;6:196
references: 19903359
references: J Virol. 2008 Jul;82(13):6610-7
references: 18417579
references: PLoS Pathog. 2008 Dec;4(12):e1000236
references: 19079577
references: J Infect Dis. 2007 Dec 15;196(12):1794-803
references: 18190260
references: Cell. 2000 Mar 3;100(5):587-97
references: 10721995
references: J Virol. 2012 Dec;86(24):13515-23
references: 23035219
references: PLoS Pathog. 2009 Jul;5(7):e1000505
references: 19578440
references: J Virol. 2007 Apr;81(8):3769-77
references: 17267484
references: J Vis Exp. 2012 Aug 22;(66):e4297
references: 22951568
references: Comp Med. 2011 Aug;61(4):330-8
references: 22330248
references: Open Immunol J. 2011;4:22-30
references: 22162983
references: Nat Immunol. 2010 May;11(5):427-34
references: 20305659
references: Comp Med. 2008 Dec;58(6):522-33
references: 19149409
references: Nat Methods. 2012 Feb 26;9(4):385-90
references: 22367054
references: J Exp Med. 2007 Aug 6;204(8):1757-64
references: 17620361
references: Nat Immunol. 2012 May;13(5):449-56
references: 22484733
references: J Exp Med. 1979 Sep 19;150(3):580-96
references: 90108
references: PLoS Pathog. 2008 Nov;4(11):e1000208
references: 19008951
references: J Virol. 2006 Jun;80(11):5104-12
references: 16698991