title: Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain.
abstract: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes various diseases, including lymphadenitis, congenital infection of fetuses and life-threatening toxoplasmic encephalitis in immunocompromised individuals. Interferon-gamma (IFN-γ)-mediated immune responses are essential for controlling tachyzoite proliferation during both acute acquired infection and reactivation of infection in the brain. Both CD4+ and CD8+ T cells produce this cytokine in response to infection, although the latter has more potent protective activity. IFN-γ can activate microglia, astrocytes and macrophages, and these activated cells control the proliferation of tachyzoites using different molecules, depending on cell type and host species. IFN-γ also has a crucial role in the recruitment of T cells into the brain after infection by inducing expression of the adhesion molecule VCAM-1 on cerebrovascular endothelial cells, and chemokines such as CXCL9, CXCL10 and CCL5. A recent study showed that CD8+ T cells are able to remove T. gondii cysts, which represent the stage of the parasite in chronic infection, from the brain through their perforin-mediated activity. Thus, the resistance to cerebral infection with T. gondii requires a coordinated network using both IFN-γ- and perforin-mediated immune responses. Elucidating how these two protective mechanisms function and collaborate in the brain against T. gondii will be crucial in developing a new method to prevent and eradicate this parasitic infection.
authors: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA. yasu.suzuki@uky.edu
authors: Yasuhiro
authors: Y
authors: Suzuki
authors: Qila
authors: Q
authors: Sa
authors: Marie
authors: M
authors: Gehman
authors: Eri
authors: E
authors: Ochiai
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000469:parasitology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060467:Disease Resistance / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D054353:Perforin / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000502:physiology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000469:parasitology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D054353:Perforin; D007371:Interferon-gamma