| First Author | Yamamoto M | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 2 | Pages | 302-13 |
| PubMed ID | 22795875 | Mgi Jnum | J:187397 |
| Mgi Id | MGI:5436356 | Doi | 10.1016/j.immuni.2012.06.009 |
| Citation | Yamamoto M, et al. (2012) A Cluster of Interferon-gamma-Inducible p65 GTPases Plays a Critical Role in Host Defense against Toxoplasma gondii. Immunity 37(2):302-313 |
| abstractText | Interferon-gamma (IFN-gamma) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-gamma upregulates approximately 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. |
