title: Differential regulation of GM1 and asialo-GM1 expression by T cells and natural killer (NK) cells in respiratory syncytial virus infection.
abstract: We previously reported that respiratory syncytial virus (RSV) infection increases lung CD8(+) T cell GM1 expression. The related lipid asialo-GM1 (ASGM1) is expressed by T cells in viral infection and by natural killer (NK) cells. The in vivo co-expression of GM1 and ASGM1 by immune cells is not defined. Here we analyzed lung lymphocyte GM1 and ASGM1 expression in RSV-infected mice. GM1 and ASGM1 were coordinately upregulated by activated CD8(+) T cells in RSV-infected BALB/c and C57BL/6 mice. In contrast, RSV infection had no effect on constitutively high NK cell GM1 expression, while increasing NK cell ASGM1 expression. GM1 and ASGM1 co-localized in lipid raft structures in NK and CD8(+) T cells sorted from the lungs of RSV-infected mice. Anti-ASGM1 Ab treatment of RSV-infected BALB/c mice depleted GM1/ASGM1-expressing NK cells and GM1/ASGM1-expressing T cells, reduced lung IFN-gamma levels, increased viral load, delayed viral clearance, and reduced illness. STAT1(-/-) mice are more susceptible to RSV replication and disease than wild-type mice. In RSV-infected STAT1(-/-) mice, anti-ASGM1 Ab altered cytokine levels, but in contrast to BALB/c mice, antibody treatment had no effect on viral load or illness. Taken together, GM1 and ASGM1 expression are differentially regulated by T and NK cells in RSV infection. Also, GM1/ASGM1-expressing cells are important for control of RSV in BALB/c mice, whereas STAT1(-/-) mice clear RSV by an alternative pathway.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chi
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Joan E
authors.initials: JE
authors.lastname: Durbin
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005677:G(M1) Ganglioside / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000628:therapy / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: D050794:STAT1 Transcription Factor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma
references.citation: J Immunol. 1986 Jun 15;136(12):4674-80
references.pmid: 3486908
references.citation: Immunopharmacology. 2000 Jul 25;48(3):237-47
references.pmid: 10960663
references.citation: J Infect Dis. 2002 May 15;185(10):1388-94
references.pmid: 11992272
references.citation: J Immunol. 2000 Feb 1;164(3):1286-92
references.pmid: 10640742
references.citation: J Interferon Cytokine Res. 2000 Apr;20(4):383-9
references.pmid: 10805373
references.citation: J Immunol. 1999 Oct 15;163(8):4109-13
references.pmid: 10510345
references.citation: Pharmacol Ther. 2006 Nov;112(2):405-24
references.pmid: 16820210
references.citation: J Virol. 2001 Apr;75(7):3152-63
references.pmid: 11238842
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12624-9
references.pmid: 11606747
references.citation: Int Immunol. 2005 Jun;17(6):749-58
references.pmid: 15967787
references.citation: Virology. 2004 Oct 1;327(2):175-85
references.pmid: 15351205
references.citation: J Immunol. 2001 Aug 1;167(3):1141-4
references.pmid: 11466327
references.citation: Virology. 2004 Dec 5;330(1):147-57
references.pmid: 15527841
references.citation: Eur J Immunol. 2002 Aug;32(8):2117-23
references.pmid: 12209623
references.citation: J Immunol. 2000 Jun 15;164(12):6480-6
references.pmid: 10843705
references.citation: Mol Immunol. 2004 Jun;41(4):399-409
references.pmid: 15163537
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):225-32
references.pmid: 11773621
references.citation: J Gen Virol. 2002 Aug;83(Pt 8):1841-1850
references.pmid: 12124448
references.citation: JAMA. 1999 Oct 20;282(15):1440-6
references.pmid: 10535434
references.citation: J Immunol. 1986 May 1;136(9):3481-5
references.pmid: 2420892
references.citation: Cell. 1996 Feb 9;84(3):443-50
references.pmid: 8608598
references.citation: Methods Mol Biol. 2000;121:163-77
references.pmid: 10818725
references.citation: J Med Virol. 1988 Oct;26(2):153-62
references.pmid: 3183639
references.citation: Biochemistry. 2002 Feb 12;41(6):1742-51
references.pmid: 11827518
references.citation: J Exp Med. 2004 Jul 19;200(2):169-79
references.pmid: 15249592
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9642-7
references.pmid: 11493690
references.citation: J Gen Virol. 1998 Nov;79 ( Pt 11):2593-601
references.pmid: 9820134
references.citation: J Supramol Struct. 1973;1(3):233-48
references.pmid: 4804838
references.citation: Virology. 2005 Jul 20;338(1):69-80
references.pmid: 15936795
references.citation: J Immunol. 2002 Mar 15;168(6):2944-52
references.pmid: 11884466
references.citation: Pediatr Res. 1990 Jan;27(1):7-10
references.pmid: 2153279
references.citation: J Immunol. 1986 Feb 15;136(4):1435-41
references.pmid: 3944461
references.citation: J Allergy Clin Immunol. 2005 Sep;116(3):550-7
references.pmid: 16159623
references.citation: J Immunol. 2000 Apr 15;164(8):4220-8
references.pmid: 10754318
references.citation: Cell. 2003 Nov 14;115(4):377-88
references.pmid: 14622593
references.citation: J Immunol. 1997 Apr 1;158(7):3070-80
references.pmid: 9120259
references.citation: J Gen Virol. 1990 Jul;71 ( Pt 7):1561-70
references.pmid: 2197371
references.citation: Semin Cell Dev Biol. 2004 Aug;15(4):397-408
references.pmid: 15207830
references.citation: Blood. 2006 Feb 1;107(3):987-93
references.pmid: 16210337
references.citation: Nat Immun Cell Growth Regul. 1985;4(1):21-39
references.pmid: 3875791
references.citation: J Biol Chem. 1997 Feb 28;272(9):5533-8
references.pmid: 9038159
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6674-9
references.pmid: 11390994
references.citation: J Immunol. 1986 Sep 1;137(5):1695-702
references.pmid: 3018079
references.citation: Philos Trans R Soc Lond B Biol Sci. 2003 May 29;358(1433):879-83
references.pmid: 12803921
references.citation: J Immunol. 2003 Dec 1;171(11):6039-45
references.pmid: 14634116
references.citation: Exp Hematol. 2000 Nov;28(11):1260-8
references.pmid: 11063874
references.citation: Cell. 1992 Feb 7;68(3):533-44
references.pmid: 1531449
references.citation: Am J Dis Child. 1986 Jun;140(6):543-6
references.pmid: 3706232
references.citation: Curr Opin Struct Biol. 2002 Oct;12(5):587-92
references.pmid: 12464309
references.citation: J Exp Med. 2004 Jan 5;199(1):25-34
references.pmid: 14699080
references.citation: Am J Respir Crit Care Med. 2003 Sep 15;168(6):633-9
references.pmid: 12773328
references.citation: J Exp Med. 1988 Sep 1;168(3):1163-8
references.pmid: 3262705
references.citation: N Engl J Med. 2001 Jun 21;344(25):1917-28
references.pmid: 11419430
references.citation: Mol Cell Biol. 2005 Jul;25(13):5456-65
references.pmid: 15964802
references.citation: J Clin Invest. 2004 May;113(10):1482-9
references.pmid: 15146246
references.citation: J Immunol. 2007 Mar 1;178(5):2651-4
references.pmid: 17312105
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
references.pmid: 11413487
references.citation: J Immunol. 1983 Sep;131(3):1531-8
references.pmid: 6309965
references.citation: J Immunol. 2004 Mar 1;172(5):3034-41
references.pmid: 14978108
references.citation: Virology. 2003 Feb 15;306(2):254-67
references.pmid: 12642099
references.citation: Lymphokine Cytokine Res. 1993 Apr;12(2):109-14
references.pmid: 8391859
references.citation: J Virol. 1985 Oct;56(1):55-9
references.pmid: 2411951
references.citation: Annu Rev Immunol. 2003;21:457-81
references.pmid: 12615889
references.citation: Infect Immun. 1979 Nov;26(2):764-6
references.pmid: 546793
references.citation: Semin Cell Dev Biol. 2004 Aug;15(4):375-87
references.pmid: 15207828
references.citation: Eur J Immunol. 2004 Sep;34(9):2579-88
references.pmid: 15307190
references.citation: Cytokine. 2000 Jul;12(7):972-85
references.pmid: 10880242
references.citation: J Immunol. 2006 Jun 15;176(12):7511-24
references.pmid: 16751398
references.citation: J Immunol. 2000 Oct 1;165(7):3571-7
references.pmid: 11034357
references.citation: J Virol. 2003 Feb;77(3):1747-56
references.pmid: 12525608
references.citation: Annu Rev Immunol. 2004;22:405-29
references.pmid: 15032583
references.citation: J Immunol. 2000 Feb 15;164(4):2009-15
references.pmid: 10657652
references.citation: J Clin Invest. 1991 Sep;88(3):1026-33
references.pmid: 1909350
references.citation: Biophys J. 2002 Nov;83(5):2693-701
references.pmid: 12414701
references.citation: J Virol. 1984 Oct;52(1):119-28
references.pmid: 6207307