A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system

Gorrell, Rebecca J., Guan, Jyeswei, Xin, Yue, Tafreshi, Mona Anoushiravani, Hutton, Melanie L., McGuckin, Michael A., Ferrero, Richard L. and Kwok, Terry (2013) A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system. Cellular Microbiology, 15 4: 554-570. doi:10.1111/cmi.12055

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Author Gorrell, Rebecca J.
Guan, Jyeswei
Xin, Yue
Tafreshi, Mona Anoushiravani
Hutton, Melanie L.
McGuckin, Michael A.
Ferrero, Richard L.
Kwok, Terry
Title A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system
Formatted title
A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system
Journal name Cellular Microbiology   Check publisher's open access policy
ISSN 1462-5814
1462-5822
Publication date 2013-04-01
Year available 2012
Sub-type Article (original research)
DOI 10.1111/cmi.12055
Volume 15
Issue 4
Start page 554
End page 570
Total pages 17
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
The type IV secretion system (T4SS) of Helicobacter pylori triggers massive inflammatory responses during gastric infection by mechanisms that are poorly understood. Here we provide evidence for a novel pathway by which the T4SS structural component, CagL, induces secretion of interleukin-8 (IL-8) independently of CagA translocation and peptidoglycan-sensing nucleotide-binding oligomerization domain 1 (NOD1) signalling. Recombinant CagL was sufficient to trigger IL-8 secretion, requiring activation of α5β1 integrin and the arginine–glycine–aspartate (RGD) motif in CagL. Mutation of the encoded RGD motif to arginine-glycine-alanine (RGA) in the cagL gene of H. pylori abrogated its ability to induce IL-8. Comparison of IL-8 induction between H. pylori ΔvirD4 strains bearing wild-type or mutant cagL indicates that CagL-dependent IL-8 induction can occur independently of CagA translocation. In line with this notion, exogenous CagL complemented H. pylori ΔcagL mutant in activating NF-κB and inducing IL-8 without restoring CagA translocation. The CagA translocation-independent, CagL-dependent IL-8induction involved host signalling via integrin α5β1, Src kinase, the mitogen-activated protein kinase (MAPK) pathway and NF-κB but was independent of NOD1. Our findings reveal a novel pathway whereby CagL, via interaction with host integrins, can trigger pro-inflammatory responses independently of CagA translocation or NOD1 signalling.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
School of Biological Sciences Publications
 
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Created: Wed, 15 Jan 2014, 03:26:03 EST by Michael Mcguckin on behalf of School of Biomedical Sciences