TY - JOUR
T1 - P62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen
AU - Lee, Youngae
AU - Sasai, Miwa
AU - Ma, Ji Su
AU - Sakaguchi, Naoya
AU - Ohshima, Jun
AU - Bando, Hironori
AU - Saitoh, Tatsuya
AU - Akira, Shizuo
AU - Yamamoto, Masahiro
N1 - Funding Information:
We thank M. Enomoto for secretarial and technical assistance. We also thank Drs. Dominique Soldati-Favre, Yoshifumi Nishikawa, and John Boothroyd for providing us with anti- T. gondii (GAP45 or GRA7) antibodies; Dr. Jonathan C. Howard for anti-Irga6 10D7 antibody and Irga6-deficient MEFs; Dr. Kiyoshi Takeda for GBP chr3 -deficient MEFs; Dr. Masaaki Komatsu for Atg7-deficient MEFs; Dr. David S. Roos for p30-OVA PruΔHX; Dr. Tsuneyasu Kaisho for CD45.1 + OT-I mice; and Dr. Jun-Ichiro Inoue for Traf6-deficient MEFs. This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas (homeostatic regulation by various types of cell death [15H01377] and Matoryoshka-type evolution [26117713]) from the Ministry of Education, Culture, Sports, Science and Technology; Cooperative Research Grant of the Institute for Enzyme Research, Joint Usage/Research Center, The University of Tokushima; The Inoue Research Award, Takeda Science Foundation; Naito Foundation; Daiichi-Sankyo Foundation of Life Science; Sumitomo Foundation; The Ichiro Kanehara Foundation for the Promotion of Medical Science and Medical Care; The Uehara Memorial Foundation; Kanae Foundation for the Promotion of Medical Research; and Research Foundation for Microbial Diseases of Osaka University.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/10/13
Y1 - 2015/10/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2015.09.005
DO - 10.1016/j.celrep.2015.09.005
M3 - Article
C2 - 26440898
AN - SCOPUS:84944076968
VL - 13
SP - 223
EP - 233
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 2
ER -