A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii

Immunity. 2012 Aug 24;37(2):302-13. doi: 10.1016/j.immuni.2012.06.009. Epub 2012 Jul 12.


Interferon-γ (IFN-γ) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-γ upregulates ∼2,000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (Gbp) family genes. We show that a cluster of Gbp genes was required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six Gbp genes located on chromosome 3 (Gbp(chr3)) by targeted chromosome engineering. Mice lacking Gbp(chr3) were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbp(chr3)-deleted macrophages were defective in IFN-γ-mediated suppression of T. gondii intracellular growth and recruitment of IFN-γ-inducible p47 GTPase Irgb6 to the parasitophorous vacuole. In addition, some members of Gbp(chr3) restored the protective response against T. gondii in Gbp(chr3)-deleted cells. Our results suggest that Gbp(chr3) play a pivotal role in anti-T. gondii host defense by controlling IFN-γ-mediated Irgb6-dependent cellular innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomes, Mammalian / genetics
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / immunology*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Immunity, Cellular / immunology
  • Immunity, Innate / immunology*
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Listeria monocytogenes / immunology
  • Luminescent Measurements
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Nitric Oxide / metabolism
  • Toxoplasma / immunology*
  • Toxoplasma / metabolism
  • Toxoplasmosis / immunology*


  • Nitric Oxide
  • Interferon-gamma
  • GTP-Binding Proteins