Bacterial Coinfection Restrains Antiviral CD8 T-cell Response via LPS-induced Inhibitory NK Cells

Nat Commun. 2018 Oct 8;9(1):4117. doi: 10.1038/s41467-018-06609-z.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology*
  • Arenaviridae Infections / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / virology
  • Coinfection / immunology*
  • Coinfection / microbiology
  • Coinfection / virology
  • Escherichia coli / immunology
  • Escherichia coli / physiology
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology
  • Host-Pathogen Interactions / immunology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / microbiology
  • Killer Cells, Natural / virology
  • Lipopolysaccharides / immunology*
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Perforin / immunology
  • Perforin / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / microbiology
  • T-Lymphocytes, Cytotoxic / virology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Lipopolysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Perforin