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.
Highlights
Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity
LPS injection significantly suppressed the anti-LCMV cytotoxic T-lymphocyte (CTL) response and increased viral burdens in the absence of NCR1 (Fig. 6i, j, l). These results demonstrate that NKG2D and NCR1 were dispensable for LPS-induced NK cell-mediated suppression of the anti-LCMV CD8 T cell immune response
This type of negative regulation of T-cells by NK cells in LCMV infection is only observed after inoculation with high virus doses (>104 pfu)[16,17,19]
Summary
Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity. 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 TLR4mediated immunoregulatory role of NK cells during viral-bacterial coinfections. The reverse scenario, i.e., the effect of a bacterial coinfection on LCMVspecific T-cell immunity, has so far only been analyzed in a polymicrobial sepsis model[8] These experiments showed that sepsis induced by cecal-ligation and puncture strongly impaired subsequent induction of a LCMV-specific CTL response[9,10,11,12]. We here demonstrate that NK cells in LPS-treated mice suppress clonal expansion of LCMV-specific CTLs by a NKG2Dindependent or NCR1-independent but perforin-dependent mechanism
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