Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria

J Immunol. 2007 Mar 1;178(5):3126-33. doi: 10.4049/jimmunol.178.5.3126.


It is known that host cells can produce type I IFNs (IFN-alphabeta) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-alphabeta signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-alphabetaR or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alphabetaR deficiency was marked, with mortality surpassing that seen in IFN-gammaR-deficient mice. Animals lacking both IFN-alphabetaR and IFN-gammaR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-alphabeta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alphabeta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alphabeta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / genetics
  • Bacteremia / immunology
  • Bacteremia / therapy
  • Bacterial Infections / genetics
  • Bacterial Infections / therapy
  • Interferon-alpha / deficiency
  • Interferon-alpha / immunology*
  • Interferon-beta / deficiency
  • Interferon-beta / immunology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Nitric Oxide / immunology
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / immunology*
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Interferon-alpha
  • Lipopolysaccharides
  • Receptors, Interferon
  • Tumor Necrosis Factor-alpha
  • interferon gamma receptor
  • Receptor, Interferon alpha-beta
  • Nitric Oxide
  • Interferon-beta
  • Interferon-gamma