Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection
- 1 September 2008
- journal article
- research article
- Published by Mary Ann Liebert Inc in Viral Immunology
- Vol. 21 (3), 327-339
- https://doi.org/10.1089/vim.2008.0003
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 up-regulated 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-γ 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.Keywords
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