| Budget Amount *help |
¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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| Research Abstract |
Interferon-g (IFN-g) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-g up-regulates ~2000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (GBP) family genes. We show that a cluster of GBP genes is required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six GBP genes located on chromosome 3 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-g-mediated suppression of T. gondii intracellular growth. In addition, some members of Gbpchr3 restored the protective response against T. gondii in Gbpchr3-deleted cells. Thus, Gbpchr3 redundantly play a pivotal role in anti-T. gondii host defense by controlling IFN-g-mediated cellular innate immunity.
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