期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 41, 页码 E5628-E5637出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1515966112
关键词
interferon; Toxoplasma; Chlamydia; GBPs; immunity-related GTPase
资金
- American Heart Association [12PRE10440003]
- National Science Foundation
- Medical Research Council (MRC)
- Boehringer Ingelheim Fonds
- Wellcome Trust
- MRC [MC_UP_1202/12]
- National Institute Health [R01AI103197]
- Medical Research Council [1243641, MC_UP_1202/12] Funding Source: researchfish
- The Francis Crick Institute [10076, 10077] Funding Source: researchfish
- MRC [MC_UP_1202/12] Funding Source: UKRI
Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFN gamma-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFN gamma prompts IRG-dependent association of Toxoplasmaand Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage of downstream PV ubiquitination and GBP delivery. Our results define a ubiquitin-centered mechanism by which host cells deliver GBPs to PVs and explain how hypervirulent parasites evade GBP-mediated immunity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据