Journal article
A cluster of interferon-γ-inducible p65 gtpases plays a critical role in host defense against toxoplasma gondii
M Yamamoto, M Okuyama, JS Ma, T Kimura, N Kamiyama, H Saiga, J Ohshima, M Sasai, H Kayama, T Okamoto, DCS Huang, D Soldati-Favre, K Horie, J Takeda, K Takeda
Immunity | CELL PRESS | Published : 2012
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 (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-medi..
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Awarded by Naito Foundation
Funding Acknowledgements
We thank C. Hidaka for excellent secretarial assistance, Y. Magota and M. Enomoto for technical assistance, and members of K.T.'s lab for discussions. Rabbit anti-Irgb6 and Irgb10 and mouse anti-Irgm3 were kindly provided by J.C. Howard. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology; Kanae Foundation for the Promotion of Medical Science; The Cell Science Research Foundation; Kato Memorial Bioscience Foundation; The Uehara Memorial Foundation; Naito Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; The Waksman Foundation of Japan Inc.; Senri Life Science Foundation; The Tokyo Biochemical Research Foundation; The Research Foundation for Microbial Diseases of Osaka University; The Nakajima Foundation; The Asahi Glass Foundation; and The Osaka Foundation for Promotion of Clinical Immunology. M.Y. and D.S.-F. are supported by the Japanese-Swiss bilateral program of The Strategic International Cooperative Program (Research Exchange Type), the Japan Science and Technology Agency (JST).