Journal article
Sensing of bacterial type IV secretion via the unfolded protein response
mBio, Vol.4(1), pp.e00418-e00412
02/19/2013
Handle:
https://hdl.handle.net/2376/102907
PMCID: PMC3624511
PMID: 23422410
Abstract
Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory responses. Ectopically expressed VceC interacted with the endoplasmic reticulum (ER) chaperone BiP/Grp78 and localized to the ER of HeLa cells. ER localization of VceC required a transmembrane domain in its N terminus. Notably, the expression of VceC resulted in reorganization of ER structures. In macrophages, VceC was required for B. abortus-induced inflammation by induction of the unfolded protein response by a process requiring inositol-requiring transmembrane kinase/endonuclease 1. Altogether, these findings suggest that translocation of the T4SS effector VceC induces ER stress, which results in the induction of proinflammatory host cell responses during B. abortus infection. IMPORTANCE Brucella species are pathogens that require a type IV secretion system (T4SS) to survive in host cells and to maintain chronic infection. By as-yet-unknown pathways, the T4SS also elicits inflammatory responses in infected cells. Here we show that inflammation caused by the T4SS results in part from the sensing of a T4SS substrate, VceC, that localizes to the endoplasmic reticulum (ER), an intracellular site of Brucella replication. Possibly via binding of the ER chaperone BiP, VceC causes ER stress with concomitant expression of proinflammatory cytokines. Thus, induction of the unfolded protein response may represent a novel pathway by which host cells can detect pathogens deploying a T4SS.
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Details
- Title
- Sensing of bacterial type IV secretion via the unfolded protein response
- Creators
- Maarten F de Jong - Department of Medical Microbiology and Immunology, University of California, Davis, California, USATregei StarrMaria G WinterAndreas B den HartighRobert ChildLeigh A KnodlerJan Maarten van DijlJean CelliRenée M Tsolis
- Publication Details
- mBio, Vol.4(1), pp.e00418-e00412
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- Intramural NIH HHS R21 AI065739 / NIAID NIH HHS AI090387 / NIAID NIH HHS R21 AI097107 / NIAID NIH HHS AI050553 / NIAID NIH HHS AI097107 / NIAID NIH HHS R01 AI050553 / NIAID NIH HHS R56 AI090387 / NIAID NIH HHS
- Identifiers
- 99900546685601842
- Language
- English
- Resource Type
- Journal article