- Brucella induction of RIDD activity promotes intracellular parasitism by subverting BLOS1-controlled immune defense Academic Article uri icon

abstract

  • Abstract The intracellular bacterial pathogen and biothreat agent Brucella is the causative agent of brucellosis, a global zoonotic disease that is associated with acute and chronic symptoms in humans and animals. The mechanisms by which the pathogen colonizes host cells remain obscure. Here, we demonstrate that infection activates the regulated IRE1-dependent decay (RIDD) of mRNA encoding BLOS1 (biogenesis of lysosome-related organelles 1 subunit 1), a protein that promotes endosome-lysosome fusion. RIDD-deficient host cells as well as mice harboring a RIDD-incompetent variant of IRE1a displayed resistance to infection. Moreover, host cells carrying a RIDD resistant variant of BLOS1 displayed enhanced trafficking of the pathogen to lysosomes, and increased resistance to intracellular parasitism. Finally, cells harboring mutations in BLOS1 displayed increased susceptibility. Taken together, the data demonstrate that host RIDD activity on BLOS1 transcripts regulate Brucella intracellular parasitism by disrupting BLOS1-directed lysosomal trafficking activity, thereby promoting maintenance of the pathogens replicative niche in the endoplasmic reticulum.

published proceedings

  • The Journal of Immunology

author list (cited authors)

  • de Figueiredo, P., Wells, K., He, K., Pandey, A., Cabello, A., Gomez, G., ... Ficht, T. A.

citation count

  • 0

complete list of authors

  • de Figueiredo, Paul||Wells, Kelsey||He, Kai||Pandey, Aseem||Cabello, Ana-Lucia||Gomez, Gabriel||Rice-FIcht, Allison||Sze, Sing-hoi||Qian, Xiaoning||Ficht, Thomas A

publication date

  • May 2020