Journal article
A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system
RJ Gorrell, J Guan, Y Xin, MA Tafreshi, ML Hutton, MA Mcguckin, RL Ferrero, T Kwok
Cellular Microbiology | WILEY-BLACKWELL | Published : 2013
DOI: 10.1111/cmi.12055
Open access
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 i..
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Awarded by NHMRC
Funding Acknowledgements
We are grateful to Mr S. Lim and Ms V. Zhang for technical assistance; Ms P. Everingham for help with data analysis using the software Linreg; the Monash Protein Purification Unit and Dr R. Law for the purification of CagL and optimization of the purification protocol respectively; Prof. David Jans and Dr Kylie APP1006010 for reagents and advice for DTAF protein labelling; Dr Judy Callaghan (Monash Micro Imaging) and Dr Marko Lampe (Leica Microsystems) for assistance with GSDIM microscopy and invaluable advice; Prof. S. Backert for providing the H. pylori strains P12, P12 Delta cagA, P12 Delta cagPAI and P1. The work was supported by NHMRC project Grants APP545983 and APP1006010, and the Victorian Government's Operational Infrastructure Support Program.