title: Accumulation of CD11b⁺Gr-1⁺ cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses.
abstract: Infection with pathogenic influenza viruses is associated with intense inflammatory disease. Here, we investigated the innate immune response in mice infected with H5N1 A/Vietnam/1203/04 and with reassortant human H1N1 A/Texas/36/91 viruses containing the virulence genes hemagglutinin (HA), neuraminidase (NA) and NS1 of the 1918 pandemic virus. Inclusion of the 1918 HA and NA glycoproteins rendered a seasonal H1N1 virus capable of inducing an exacerbated host innate immune response similar to that observed for highly pathogenic A/Vietnam/1203/04 virus. Infection with 1918 HA/NA:Tx/91 and A/Vietnam/1203/04 were associated with severe lung pathology, increased cytokine and chemokine production, and significant immune cell changes, including the presence of CD11b(+)Gr-1(+) cells in the blood, lung and bone marrow. Significant differential gene expression in the lung included pathways for cell death, apoptosis, production and response to reactive oxygen radicals, as well as arginine and proline metabolism and chemokines associated with monocyte and neutrophil/granulocyte accumulation and/or activation. Arginase was produced in the lung of animals infected with A/Vietnam/1204. These results demonstrate that the innate immune cell response results in the accumulation of CD11b(+)Gr-1(+) cells and products that have previously been shown to contribute to T cell suppression.
authors: Battelle, 505 King Avenue, Columbus, OH 43201, USA. longj@battelle.org
authors: James P
authors: JP
authors: Long
authors: Mark S
authors: MS
authors: Kotur
authors: Gregory V
authors: GV
authors: Stark
authors: Richard L
authors: RL
authors: Warren
authors: Manjula
authors: M
authors: Kasoji
authors: Jeremy L
authors: JL
authors: Craft
authors: Randy A
authors: RA
authors: Albrecht
authors: Adolfo
authors: A
authors: García-Sastre
authors: Michael G
authors: MG
authors: Katze
authors: Katrina M
authors: KM
authors: Waters
authors: Daphne
authors: D
authors: Vasconcelos
authors: Patrick J
authors: PJ
authors: Sabourin
authors: Herbert S
authors: HS
authors: Bresler
authors: Carol L
authors: CL
authors: Sabourin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006098:Granulocytes / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D014774:Virulence / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D018925:Chemokines
references: PLoS Pathog. 2008 Aug 01;4(8):e1000115
references: 18670648
references: J Virol. 2004 Sep;78(17):9499-511
references: 15308742
references: Nat Rev Immunol. 2009 Mar;9(3):162-74
references: 19197294
references: J Immunol. 2000 Dec 15;165(12):6723-30
references: 11120790
references: J Infect Dis. 2007 Apr 1;195(7):1018-28
references: 17330793
references: J Clin Invest. 2008 Dec;118(12):4036-48
references: 19033672
references: J Immunol. 1998 Nov 15;161(10):5313-20
references: 9820504
references: Med Microbiol Immunol. 2010 Aug;199(3):273-81
references: 20376485
references: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2746-51
references: 11226311
references: J Virol. 2005 Dec;79(23):14933-44
references: 16282492
references: J Virol. 1999 Nov;73(11):9679-82
references: 10516084
references: Science. 2005 Oct 7;310(5745):77-80
references: 16210530
references: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3455-60
references: 19218453
references: J Exp Med. 2007 Jun 11;204(6):1463-74
references: 17548519
references: Emerg Infect Dis. 2006 Jan;12(1):15-22
references: 16494711
references: J Virol. 2010 Aug;84(15):7613-24
references: 20504916
references: N Engl J Med. 2004 Mar 18;350(12):1179-88
references: 14985470
references: J Exp Med. 2005 Apr 18;201(8):1257-68
references: 15824085
references: Annu Rev Immunol. 1992;10:123-51
references: 1534240
references: PLoS Pathog. 2011 Jan 27;7(1):e1001218
references: 21298032
references: J Virol. 2000 Jul;74(13):6105-16
references: 10846094
references: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3064-9
references: 18287069
references: Blood. 2006 Sep 1;108(5):1627-34
references: 16709924
references: Nat Med. 2006 Oct;12(10):1203-7
references: 16964257
references: J Hematol Oncol. 2008 Sep 25;1:14
references: 18817562
references: PLoS Pathog. 2010 Jun 17;6(6):e1000899
references: 20585552
references: J Leukoc Biol. 2004 Oct;76(4):886-95
references: 15240757
references: J Biol Chem. 2002 Jun 14;277(24):21123-9
references: 11950832
references: J Immunol. 2009 Apr 15;182(8):4499-506
references: 19342621
references: J Nutr. 2004 Oct;134(10 Suppl):2830S-2836S; discussion 2853S
references: 15465795
references: Immunol Rev. 1997 Oct;159:95-103
references: 9416505