Gamma interferon production by hepatic NK T cells during Escherichia coli infection is resistant to the inhibitory effects of oxidative stress

Infect Immun. 2003 May;71(5):2468-77. doi: 10.1128/IAI.71.5.2468-2477.2003.

Abstract

The reductive-oxidative status of tissues regulates the expression of many inflammatory genes that are induced during gram-negative bacterial infections. The cytokine gamma interferon (IFN-gamma) is a potent stimulus for host inflammatory gene expression, and oxidative stress has been shown to inhibit its production in mice challenged with Escherichia coli bacteria. The objective of the present study was to characterize the cells that produced IFN-gamma in a mouse bacterial peritonitis model and determine the effects of oxidative stress on their activation. The liver contained large numbers of IFN-gamma-expressing lymphocytes following challenge with viable E. coli bacteria. The surface phenotypes of IFN-gamma-expressing hepatic lymphocytes were those of natural killer (NK) cells (NK1.1(+) CD3(-)), conventional T cells (NK1.1(-) CD3(+)), and NK T cells (NK1.1(+) CD3(+)). Treating mice with diethyl maleate to deplete tissue thiols significantly impaired IFN-gamma production by NK cells, conventional T cells, and CD1d-restricted NK T cells in response to E. coli challenge. However, IFN-gamma expression by a subset of NK T cells, which did not bind alpha-galactosylceramide-CD1d tetramers, was resistant to the inhibitory effects of tissue oxidative stress. Stress-resistant IFN-gamma-expressing cells were also predominantly CD8(+) and bore gamma delta T-cell antigen receptors. The residual IFN-gamma response by NK T cells may explain previous reports of hepatic gene expression following gram-negative bacterial challenge in thiol-depleted mice. The finding also demonstrates that innate immune cells differ significantly in their responses to altered tissue redox status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / metabolism
  • Female
  • Immunophenotyping
  • Interferon-gamma / biosynthesis*
  • Killer Cells, Natural / metabolism*
  • Liver / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress*
  • Receptors, Antigen, T-Cell, gamma-delta / analysis

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Interferon-gamma