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Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense

التفاصيل البيبلوغرافية
العنوان: Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense
المؤلفون: Kelsey Michelle Wells, Kai He, Aseem Pandey, Ana Cabello, Dongmei Zhang, Jing Yang, Gabriel Gomez, Yue Liu, Haowu Chang, Xueqiang Li, Hao Zhang, Xuehuang Feng, Luciana Fachini da Costa, Richard Metz, Charles D Johnson, Cameron Lee Martin, Jill Skrobarczyk, Luc R Berghman, Kristin L Patrick, Julian Leibowitz, Allison Ficht, Sing-Hoi Sze, Jianxun Song, Xiaoning Qian, Qing-Ming Qin, Thomas A Ficht, Paul de Figueiredo
المصدر: eLife, Vol 11 (2022)
بيانات النشر: eLife Sciences Publications Ltd, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: Brucella, coronavirus, regulated IRE1α-dependent decay (RIDD), BLOS1, Brucella-containing vacuoles/lysosomes (BCVs), intracellular parasitism, Medicine, Science, Biology (General), QH301-705.5
الوصف: The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome–lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD–BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/73625; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.73625
URL الوصول: https://doaj.org/article/d0a8cb3ad2ef4a8c88d27a290700c019
رقم الأكسشن: edsdoj.0a8cb3ad2ef4a8c88d27a290700c019
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.73625