title: Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication.
abstract: IFN-γ orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the C-terminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene,  Heinrich-Heine-University Duesseldorf, Duesseldorf 40225,  Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Degrandi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kravets
authors.forename: Carolin
authors.initials: C
authors.lastname: Konermann
authors.forename: Cornelia
authors.initials: C
authors.lastname: Beuter-Gunia
authors.forename: Verena
authors.initials: V
authors.lastname: Klümpers
authors.forename: Sarah
authors.initials: S
authors.lastname: Lahme
authors.forename: Eva
authors.initials: E
authors.lastname: Rasch
authors.forename: Anne K
authors.initials: AK
authors.lastname: Mausberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer-Hammer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D001253:Astrocytes; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007371:Interferon-gamma / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D012098:Reproduction / Q000502:physiology; D014122:Toxoplasma / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
chemical_list: D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C452200:Gbp2 protein, mouse