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A Cluster of Interferon-γ-Inducible p65 GTPases Plays a Critical Role in Host Defense against Toxoplasma gondii. (Masahiro YAMAMOTO & Kiyoshi TAKEDA in Immunity)
Interferon-γ (IFN-γ) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-γ up-regulates ~2000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (GBP) family genes.
The authors show that a cluster of GBP genes was required for host cellular immunity against the intracellular parasite Toxoplasma gondii.
The authors generated mice deficient for all six GBP genes located on chromosome 3 (Gbpchr3) by targeted chromosome engineering. Mice lacking Gbpchr3 were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbpchr3-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 Gbpchr3 restored the protective response against T. gondii in Gbpchr3-deleted cells.
These results suggest that Gbpchr3 play a pivotal role in anti-T. gondii host defense by controlling IFN-γ-mediated Irgb6-dependent cellular innate immunity.
Immunology Frontier Research Center (WPI-IFReC), Osaka University