title: Mechanisms of interferon-beta-induced inhibition of Toxoplasma gondii growth in murine macrophages and embryonic fibroblasts: role of immunity-related GTPase M1.
abstract: The apical complex of Toxoplasma gondii enables it to invade virtually all nucleated cells in warm-blooded animals, including humans, making it a parasite of global importance. Anti-T. gondii cellular defence mechanisms depend largely on interferon (IFN)-γ production by immune cells. However, the molecular mechanism of IFN-β-mediated defence remains largely unclear. Here, mouse peritoneal macrophages and murine embryonic fibroblasts (MEFs) primed with recombinant IFN-β and IFN-γ showed different pathways of activation. Treatment of these cells with IFN-β or IFN-γ inhibited T. gondii (type II PLK strain) growth. Priming macrophages with IFN-β had no effect on inflammatory cytokine expression, inducible nitric oxide synthase or indoleamine 2,3-dioxygenase, nor did it have an effect on their metabolites, nitric oxide and kynurenine respectively. In contrast, IFN-γ stimulation was characterized by classical macrophage activation and T. gondii elimination. IFN-β activation recruited the immunity-related GTPase M1 (IRGM1) to the parasitophorous vacuole in the macrophages and MEFs. Anti-toxoplasma activities induced by IFN-β were significantly reduced after IRGM1 knockdown in murine macrophages and in IRGM1-deficient MEFs. Thus, this study unravels an alternative pathway of macrophage activation by IFN-β and provides a mechanistic explanation for the contribution of IRGM1 induced by IFN-β to the elimination of T. gondii.
authors: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.|Department of Animal Behavior, Management, Genetics and Breeding, Faculty of Veterinary Medicine, Sohag University, Sohag City, Sohag, 82524, Egypt.
authors: Motamed Elsayed
authors: ME
authors: Mahmoud
authors: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
authors: Fumiki
authors: F
authors: Ui
authors: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.|Department of Animal Medicine, Faculty of Veterinary Medicine, Sohag University, Sohag City, Sohag, 82524, Egypt.
authors: Doaa
authors: D
authors: Salman
authors: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
authors: Maki
authors: M
authors: Nishimura
authors: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.
authors: Yoshifumi
authors: Y
authors: Nishikawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology* / Q000469:parasitology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D016899:Interferon-beta / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D014122:Toxoplasma / Q000254:growth & development* / Q000276:immunology*; D014617:Vacuoles / Q000378:metabolism / Q000469:parasitology
chemical_list: C096000:Ifi1 protein, mouse; D016899:Interferon-beta; D007371:Interferon-gamma; D019204:GTP-Binding Proteins