Confounding Roles for Type I Interferons During Bacterial and Viral Pathogenesis

Int Immunol. 2013 Dec;25(12):663-9. doi: 10.1093/intimm/dxt050. Epub 2013 Oct 24.

Abstract

Although type I interferons (IFN-I) were initially defined as potent antiviral agents, they can also cause decreased host resistance to some bacterial and viral infections. The many antiviral functions of the IFN-I include direct suppression of viral replication and activation of the immune response against viruses. In addition to their antiviral effects, IFN-I are also protective against several extracellular bacterial infections, in part, by promoting the induction of TNF-α and nitric oxide. In contrast, there is a negative effect of IFN-I on host resistance during chronic infection with lymphocytic choriomeningitis virus (LCMV) and acute infections with intracellular bacteria. In the case of LCMV, chronic IFN-I signaling induces adaptive immune system suppression. Blockade of IFN-I signaling removes the suppression and allows CD4 T-cell- and IFN-γ-mediated resolution of the infection. During acute intracellular bacterial infection, IFN-I suppress innate immunity by at least two defined mechanisms. During Francisella infection, IFN-I prevent IL-17 upregulation on γδ T cells and neutrophil recruitment. Following Listeria infection, IFN-I promote the cell death of macrophages and lymphocytes, which leads to innate immune suppression. These divergent findings for the role of IFN-I on pathogen control emphasize the complexity of the interferons system and force more mechanistic evaluation of its role in pathogenesis. This review evaluates IFN-I during infection with an emphasis on work carried out IFN-I-receptor-deficient mice.

Keywords: LCMV; Listeria monocytogenes; cytokine; infection; mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism*
  • Disease Models, Animal
  • Extracellular Space / immunology
  • Extracellular Space / metabolism
  • Extracellular Space / microbiology
  • Immunity, Innate
  • Interferon Type I / immunology
  • Interferon Type I / metabolism*
  • Intracellular Space / immunology
  • Intracellular Space / metabolism
  • Intracellular Space / microbiology
  • Listeria monocytogenes / immunology
  • Listeriosis / genetics
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction
  • Virus Diseases / genetics
  • Virus Diseases / immunology
  • Virus Diseases / metabolism*

Substances

  • Interferon Type I
  • Receptor, Interferon alpha-beta