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Title

A Cluster of Interferon-γ-Inducible p65 GTPases Plays a Critical Role in Host Defense against Toxoplasma gondii

Authors
Yamamoto, Masahiro
Okuyama, Megumi
Ma, Ji Su
Kimura, Taishi
Kamiyama, Naganori
Saiga, Hiroyuki
Ohshima, Jun
Sasai, Miwa
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Published in Immunity. 2012, vol. 37, no. 2, p. 302-313
Abstract 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.
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PMID: 22795875
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Article (Author postprint) (4.1 MB) - public document Free access
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Research group Biologie d'un parasite intracellulaire obligatoire (773)
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YAMAMOTO, Masahiro et al. A Cluster of Interferon-γ-Inducible p65 GTPases Plays a Critical Role in Host Defense against Toxoplasma gondii. In: Immunity, 2012, vol. 37, n° 2, p. 302-313. https://archive-ouverte.unige.ch/unige:23058

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Deposited on : 2012-09-27

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