title: Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii.
abstract: In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations, including LPS. However, the physiological role of IFN-γ production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b(+) cells suggested that IFN-γ production by microglia, which is the only CD11b(+) cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-γ produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Qila
authors.initials: Q
authors.lastname: Sa
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Eri
authors.initials: E
authors.lastname: Ochiai
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Ashish
authors.initials: A
authors.lastname: Tiwari
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Sara
authors.initials: S
authors.lastname: Perkins
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Jeremi
authors.initials: J
authors.lastname: Mullins
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
authors.forename: Marie
authors.initials: M
authors.lastname: Gehman
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: William
authors.initials: W
authors.lastname: Huckle
authors.affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;
authors.forename: Willard H
authors.initials: WH
authors.lastname: Eyestone
authors.affiliation: Transgenic Animal Model Core, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109; and.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.affiliation: Department of Biostatistics, University of Kentucky College of Public Health, Lexington, KY 40504.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Shelton
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061; yasu.suzuki@uky.edu.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000469:parasitology; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D017628:Microglia / Q000276:immunology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D007371:Interferon-gamma