Differential regulation of GM1 and asialo-GM1 expression by T cells and natural killer (NK) cells in respiratory syncytial virus infection.
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.
Moore
Martin L
ML
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
Chi
Michael H
MH
Goleniewska
Kasia
K
Durbin
Joan E
JE
Peebles
R Stokes
RS
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
D050794:STAT1 Transcription Factor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma
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