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Infection and Immunity, June 2005, p. 3278-3286, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3278-3286.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

p47 GTPases Regulate Toxoplasma gondii Survival in Activated Macrophages

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York,¹ Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, North Carolina,² Departments of Medicine and Immunology, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina,³ Department of Medicine, Division of Hematology, Duke University and Durham VA Medical Centers, Durham, North Carolina,⁴ Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland⁵

Received 20 August 2004/ Returned for modification 29 September 2004/ Accepted 2 February 2005

The cytokine gamma interferon (IFN-) is critical for resistance to Toxoplasma gondii. IFN- strongly activates macrophages and nonphagocytic host cells to limit intracellular growth of T. gondii; however, the cellular factors that are required for this effect are largely unknown. We have shown previously that IGTP and LRG-47, members of the IFN--regulated family of p47 GTPases, are required for resistance to acute T. gondii infections in vivo. In contrast, IRG-47, another member of this family, is not required. In the present work, we addressed whether these GTPases are required for IFN--induced suppression of T. gondii growth in macrophages in vitro. Bone marrow macrophages that lacked IGTP or LRG-47 displayed greatly attenuated IFN--induced inhibition of T. gondii growth, while macrophages that lacked IRG-47 displayed normal inhibition. Thus, the ability of the p47 GTPases to limit acute infection in vivo correlated with their ability to suppress intracellular growth in macrophages in vitro. Using confocal microscopy and sucrose density fractionation, we demonstrated that IGTP largely colocalizes with endoplasmic reticulum markers, while LRG-47 was mainly restricted to the Golgi. Although both IGTP and LRG-47 localized to vacuoles containing latex beads, neither protein localized to vacuoles containing live T. gondii. These results suggest that IGTP and LRG-47 are able to regulate host resistance to acute T. gondii infections through their ability to inhibit parasite growth within the macrophage.

Editor: J. L. Flynn

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