Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response

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...

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Autores principales:	Maarten F. de Jong, Tregei Starr, Maria G. Winter, Andreas B. den Hartigh, Robert Child, Leigh A. Knodler, Jan Maarten van Dijl, Jean Celli, Renée M. Tsolis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/708e716606f1474fb06f4ac852025a7a
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spelling	oai:doaj.org-article:708e716606f1474fb06f4ac852025a7a2021-11-15T15:40:22ZSensing of Bacterial Type IV Secretion via the Unfolded Protein Response10.1128/mBio.00418-122150-7511https://doaj.org/article/708e716606f1474fb06f4ac852025a7a2013-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00418-12https://doaj.org/toc/2150-7511ABSTRACT 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.Maarten F. de JongTregei StarrMaria G. WinterAndreas B. den HartighRobert ChildLeigh A. KnodlerJan Maarten van DijlJean CelliRenée M. TsolisAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 1 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Maarten F. de Jong Tregei Starr Maria G. Winter Andreas B. den Hartigh Robert Child Leigh A. Knodler Jan Maarten van Dijl Jean Celli Renée M. Tsolis Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
description	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.
format	article
author	Maarten F. de Jong Tregei Starr Maria G. Winter Andreas B. den Hartigh Robert Child Leigh A. Knodler Jan Maarten van Dijl Jean Celli Renée M. Tsolis
author_facet	Maarten F. de Jong Tregei Starr Maria G. Winter Andreas B. den Hartigh Robert Child Leigh A. Knodler Jan Maarten van Dijl Jean Celli Renée M. Tsolis
author_sort	Maarten F. de Jong
title	Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
title_short	Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
title_full	Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
title_fullStr	Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
title_full_unstemmed	Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response
title_sort	sensing of bacterial type iv secretion via the unfolded protein response
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/708e716606f1474fb06f4ac852025a7a
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Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response

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