title: The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells.
abstract: Highly pathogenic avian influenza H5N1 epidemics are a significant public health hazard. Genetically engineered H5N1 viruses with mammalian transmission activity highlight the potential risk of a human influenza H5N1 pandemic. Understanding the underlying principles of the innate immune system in response to influenza H5N1 viruses will lead to improved prevention and control of these potentially deadly viruses. γδ T cells act as the first line of defense against microbial infection and help initiate adaptive immune responses during the early stages of viral infection. In this study, we investigated the molecular mechanisms of γδ T cells in response to influenza H5N1 viral infection. We found that recombinant hemagglutinin (rHA) derived from three different strains of influenza H5N1 viruses elicited the activation of γδ T cells cultured in peripheral blood mononuclear cells (PBMCs). Both the cell surface expression of CD69, an early activation marker on γδ T cells, and the production of interferon-γ (IFN-γ) were significantly increased. Notably, the rHA protein-induced γδ T-cell activation was not mediated by TCRγδ, NKG2D or pattern recognition receptors (PRRs) or NKp46 receptors. The interaction of rHA proteins with sialic acid receptors may play a critical role in γδ T-cell activation. Our data may provide insight into the mechanisms underlying γδ T-cell activation in response to infection with H5N1 viruses.
authors.forename: Yanlai
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Lianxian
authors.initials: L
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015415:Biomarkers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface; D051192:Receptors, Pattern Recognition; D011994:Recombinant Proteins; C092488:sialic acid receptor; D007371:Interferon-gamma
references.citation: Wkly Epidemiol Rec. 2012 Mar 30;87(13):117-23
references.pmid: 24340397
references.citation: Cell Mol Immunol. 2012 Jan;9(1):34-44
references.pmid: 21666706
references.citation: Nature. 2012 Jun 20;486(7403):335-40
references.pmid: 22722191
references.citation: Cell Mol Immunol. 2013 Jan;10(1):58-64
references.pmid: 23147720
references.citation: Nature. 2006 Mar 23;440(7083):435-6
references.pmid: 16554799
references.citation: Science. 2009 Jul 10;325(5937):197-201
references.pmid: 19465683
references.citation: Nature. 2001 Jun 14;411(6839):820-4
references.pmid: 11459064
references.citation: Biosecur Bioterror. 2012 Mar;10(1):151-2
references.pmid: 22176667
references.citation: Springer Semin Immunopathol. 1999;21(1):55-75
references.pmid: 10389232
references.citation: Nature. 1998 Jan 29;391(6666):502-6
references.pmid: 9461220
references.citation: Cell Mol Immunol. 2013 Jan;10(1):30-4
references.pmid: 23085943
references.citation: Cancer Lett. 2008 Dec 18;272(2):242-52
references.pmid: 18782650
references.citation: J Virol. 2013 Mar;87(6):3571-7
references.pmid: 23269809
references.citation: Cell Mol Immunol. 2013 Jan;10(1):35-41
references.pmid: 23241899
references.citation: Science. 2006 Apr 21;312(5772):399
references.pmid: 16556800
references.citation: Cancer Res. 2007 Jan 1;67(1):5-8
references.pmid: 17210676
references.citation: J Exp Med. 2011 Jan 17;208(1):181-93
references.pmid: 21220454
references.citation: Curr Opin Immunol. 2006 Oct;18(5):539-46
references.pmid: 16870417
references.citation: J Virol. 2011 Oct;85(19):10109-16
references.pmid: 21752902
references.citation: J Immunol. 2010 Jul 1;185(1):55-63
references.pmid: 20511557
references.citation: MMWR Morb Mortal Wkly Rep. 2007 Aug 10;56(31):789-94
references.pmid: 17687244
references.citation: Cell Mol Immunol. 2013 Jan;10(1):13-20
references.pmid: 23085946
references.citation: J Immunol. 2005 Aug 15;175(4):2144-51
references.pmid: 16081780
references.citation: Anticancer Res. 2010 Nov;30(11):4509-13
references.pmid: 21115900
references.citation: Gastric Cancer. 2012 Oct;15(4):433-9
references.pmid: 22252158
references.citation: Curr Opin Immunol. 2006 Feb;18(1):31-8
references.pmid: 16337364
references.citation: Int Immunol. 2010 Apr;22(4):299-306
references.pmid: 20181655
references.citation: Proc Natl Acad Sci U S A. 1969 Oct;64(2):634-41
references.pmid: 5261039
references.citation: J Infect Dis. 2009 Sep 15;200(6):858-65
references.pmid: 19656068
references.citation: Cell Host Microbe. 2010 Jun 25;7(6):440-51
references.pmid: 20542248
references.citation: Nature. 2012 May 02;486(7403):420-8
references.pmid: 22722205
references.citation: Int Immunopharmacol. 2011 Oct;11(10):1399-406
references.pmid: 21624505
references.citation: J Virol. 2013 Feb;87(4):2215-25
references.pmid: 23221567
references.citation: Arch Virol. 2011 Oct;156(10):1803-12
references.pmid: 21744000
references.citation: Science. 2012 Jun 22;336(6088):1534-41
references.pmid: 22723413
references.citation: Nature. 1988 Jun 2;333(6172):426-31
references.pmid: 3374584
references.citation: Cell Immunol. 2010;264(1):71-7
references.pmid: 20483407
references.citation: J Exp Med. 1994 Jan 1;179(1):323-8
references.pmid: 8270877
references.citation: Cell Mol Immunol. 2011 Nov;8(6):462-8
references.pmid: 21946434
references.citation: J Virol. 2010 Aug;84(15):7822-31
references.pmid: 20484512
references.citation: Front Biosci. 2005 Sep 01;10:2676-700
references.pmid: 15970527
references.citation: J Gen Virol. 1988 Nov;69 ( Pt 11):2785-95
references.pmid: 3183628
references.citation: Nature. 2001 Feb 22;409(6823):1055-60
references.pmid: 11234016
references.citation: Scand J Immunol. 2012 Sep;76(3):213-22
references.pmid: 22670577
references.citation: PLoS One. 2011;6(6):e21183
references.pmid: 21731666
references.citation: Viruses. 2012 Dec;4(12):3363-88
references.pmid: 23342363
references.citation: J Virol. 2011 Dec;85(24):13463-7
references.pmid: 21994454
references.citation: J Immunol. 2011 Jun 15;186(12):6693-700
references.pmid: 21562160
references.citation: Cell Mol Immunol. 2013 Jan;10(1):50-7
references.pmid: 23064104
references.citation: Eur Respir J. 2006 Sep;28(3):622-6
references.pmid: 16946093
references.citation: Immunol Lett. 2011 Mar 30;135(1-2):59-63
references.pmid: 20923686