Negative impact of IFN-γ on early host immune responses to retroviral infection

J Immunol. 2012 Sep 1;189(5):2521-9. doi: 10.4049/jimmunol.1201125. Epub 2012 Jul 20.

Abstract

The immune system is tasked with defending against a myriad of microbial infections, and its response to a given infectious microbe may be strongly influenced by coinfection with another microbe. It was shown that infection of mice with lactate dehydrogenase-elevating virus (LDV) impairs early adaptive immune responses to Friend virus (FV) coinfection. To investigate the mechanism of this impairment, we examined LDV-induced innate immune responses and found LDV-specific induction of IFN-α and IFN-γ. LDV-induced IFN-α had little effect on FV infection or immune responses, but unexpectedly, LDV-induced IFN-γ production dampened Th1 adaptive immune responses and enhanced FV infection. Two distinct effects were identified. First, LDV-induced IFN-γ signaling indirectly modulated FV-specific CD8+ T cell responses. Second, intrinsic IFN-γ signaling in B cells promoted polyclonal B cell activation and enhanced early FV infection, despite promotion of germinal center formation and neutralizing Ab production. Results from this model reveal that IFN-γ production can have detrimental effects on early adaptive immune responses and virus control.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity* / genetics
  • Animals
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Female
  • Friend murine leukemia virus / immunology
  • Friend murine leukemia virus / pathogenicity
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Lactate dehydrogenase-elevating virus / immunology
  • Lactate dehydrogenase-elevating virus / pathogenicity
  • Leukemia Virus, Murine / immunology*
  • Leukemia Virus, Murine / pathogenicity
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / immunology
  • Leukemia, Experimental / virology
  • Mice
  • Mice, Congenic
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Retroviridae Infections / genetics
  • Retroviridae Infections / immunology*
  • Retroviridae Infections / pathology
  • Spleen Focus-Forming Viruses / immunology
  • Spleen Focus-Forming Viruses / pathogenicity
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / virology

Substances

  • Interferon-gamma