p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen
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 vacuo...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2015-10-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715010165 |
id |
doaj-f7c7545e1935400d89b4106e5ebafe38 |
---|---|
record_format |
Article |
spelling |
doaj-f7c7545e1935400d89b4106e5ebafe382020-11-25T01:15:01ZengElsevierCell Reports2211-12472015-10-0113222323310.1016/j.celrep.2015.09.005p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar AntigenYoungae Lee0Miwa Sasai1Ji Su Ma2Naoya Sakaguchi3Jun Ohshima4Hironori Bando5Tatsuya Saitoh6Shizuo Akira7Masahiro Yamamoto8Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanDepartment of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, JapanAlso 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.http://www.sciencedirect.com/science/article/pii/S2211124715010165 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Youngae Lee Miwa Sasai Ji Su Ma Naoya Sakaguchi Jun Ohshima Hironori Bando Tatsuya Saitoh Shizuo Akira Masahiro Yamamoto |
spellingShingle |
Youngae Lee Miwa Sasai Ji Su Ma Naoya Sakaguchi Jun Ohshima Hironori Bando Tatsuya Saitoh Shizuo Akira Masahiro Yamamoto p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen Cell Reports |
author_facet |
Youngae Lee Miwa Sasai Ji Su Ma Naoya Sakaguchi Jun Ohshima Hironori Bando Tatsuya Saitoh Shizuo Akira Masahiro Yamamoto |
author_sort |
Youngae Lee |
title |
p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen |
title_short |
p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen |
title_full |
p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen |
title_fullStr |
p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen |
title_full_unstemmed |
p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen |
title_sort |
p62 plays a specific role in interferon-γ-induced presentation of a toxoplasma vacuolar antigen |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-10-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715010165 |
work_keys_str_mv |
AT youngaelee p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT miwasasai p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT jisuma p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT naoyasakaguchi p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT junohshima p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT hironoribando p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT tatsuyasaitoh p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT shizuoakira p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen AT masahiroyamamoto p62playsaspecificroleininterferonginducedpresentationofatoxoplasmavacuolarantigen |
_version_ |
1725154839214686208 |