Abstract
Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity. Infections in the real world, however, are often accompanied by coinfections with unrelated pathogens. Here we show that in mice, systemic coinfection with E. coli suppresses the LCMV-specific cytotoxic T-lymphocyte (CTL) response and virus elimination in a NK cell- and TLR2/4-dependent manner. Soluble TLR4 ligand LPS also induces NK cell-mediated negative CTL regulation during LCMV infection. NK cells in LPS-treated mice suppress clonal expansion of LCMV-specific CTLs by a NKG2D- or NCR1-independent but perforin-dependent mechanism. These results suggest a TLR4-mediated immunoregulatory role of NK cells during viral-bacterial coinfections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arenaviridae Infections / immunology*
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Arenaviridae Infections / virology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / microbiology
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CD8-Positive T-Lymphocytes / virology
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Coinfection / immunology*
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Coinfection / microbiology
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Coinfection / virology
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Escherichia coli / immunology
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Escherichia coli / physiology
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Escherichia coli Infections / immunology*
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Escherichia coli Infections / microbiology
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Host-Pathogen Interactions / immunology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / microbiology
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Killer Cells, Natural / virology
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Lipopolysaccharides / immunology*
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Lymphocytic choriomeningitis virus / immunology
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Lymphocytic choriomeningitis virus / physiology
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Perforin / immunology
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Perforin / metabolism
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / microbiology
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T-Lymphocytes, Cytotoxic / virology
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Toll-Like Receptor 4 / immunology
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Toll-Like Receptor 4 / metabolism
Substances
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Lipopolysaccharides
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Perforin