title: p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen.
abstract: Also known as Sqstm1, p62 is a selective autophagy adaptor with a ubiquitin-binding domain. However, the role of p62 in the host defense against Toxoplasma gondii infection is unclear. Here, we show that interferon γ (IFN-γ) stimulates ubiquitin and p62 recruitment to T. gondii parasitophorous vacuoles (PVs). Some essential autophagy-related proteins, but not all, are required for this recruitment. Regardless of normal IFN-γ-induced T. gondii clearance activity and ubiquitination, p62 deficiency in antigen-presenting cells (APCs) and mice diminishes the robust IFN-γ-primed activation of CD8(+) T cells that recognize the T. gondii-derived antigen secreted into PVs. Because the expression of Atg3 and Irgm1/m3 in APCs is essential for PV disruption, ubiquitin and p62 recruitment, and vacuolar-antigen-specific CD8(+) T cell activation, IFN-γ-mediated ubiquitination and the subsequent recruitment of p62 to T. gondii are specifically required for the acquired immune response after PV disruption by IFN-γ-inducible GTPases.
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Youngae
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Sasai
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Ma
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohshima
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Bando
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Division of Molecular Genetics, Institute for Enzyme Research, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: myamamoto@biken.osaka-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D001343:Autophagy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D000071456:Sequestosome-1 Protein; D014122:Toxoplasma / Q000276:immunology*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014617:Vacuoles / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000953:Antigens, Protozoan; D006360:Heat-Shock Proteins; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D025801:Ubiquitin; D007371:Interferon-gamma