ID: 260. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Coers, Jörn
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 112
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.256
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">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<italic>γ</italic>-inducible GBP and 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<italic>γ</italic> results in IRG-dependent ubiquitination of Toxoplasma- and Chlamydia-containing vacuoles through regulated translocation of the E3 ubiquitin ligase 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 an ubiquitin-centered mechanism by which host cells deliver GBPs to PVs and explain how hypervirulent parasites evade GBP-mediated immunity.</p> </sec> </abstract>