期刊
IMMUNITY
卷 37, 期 2, 页码 302-313出版社
CELL PRESS
DOI: 10.1016/j.immuni.2012.06.009
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资金
- Ministry of Education, Culture, Sports, Science and Technology
- Kanae Foundation for the Promotion of Medical Science
- Cell Science Research Foundation
- Kato Memorial Bioscience Foundation
- Uehara Memorial Foundation
- Naito Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Waksman Foundation of Japan Inc.
- Senri Life Science Foundation
- Tokyo Biochemical Research Foundation
- Research Foundation for Microbial Diseases of Osaka University
- Nakajima Foundation
- Asahi Glass Foundation
- Osaka Foundation for Promotion of Clinical Immunology
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [24390120] Funding Source: KAKEN
Interferon-gamma (IFN-gamma) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-gamma upregulates similar to 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-gamma-mediated suppression of T. gondii intracellular growth and recruitment of IFN-gamma-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-gamma-mediated Irgb6-dependent cellular innate immunity.
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