A novel NOD1‐ and CagA‐independent pathway of interleukin‐8 induction mediated by the Helicobacter pylori type IV secretion system. (21st November 2012)

• Record Type: Journal Article
• Authors: Gorrell, Rebecca J.; Guan, Jyeswei; Xin, Yue; Tafreshi, Mona Anoushiravani; Hutton, Melanie L.; McGuckin, Michael A.; Ferrero, Richard L.; Kwok, Terry
• Is Part Of: Cellular microbiology. Volume 15:Number 4(2013:Apr.)
• Page Start: 554
• Page End: 570
• Publication Date: 2012-11-21
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12055
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The type IV secretion system (T4SS) of <italic>Helicobacter pylori</italic> 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 α<sub>5</sub>β<sub>1</sub> integrin and the arginine–glycine–aspartate (RGD) motif in CagL. Mutation of the encoded RGD motif to arginine‐glycine‐alanine (RGA) in the <italic>cagL</italic> gene of <italic>H. pylori</italic> abrogated its ability to induce IL‐8. Comparison of IL‐8 induction between <italic>H. pylori</italic> Δ<italic>virD4</italic> strains bearing wild‐type or mutant <italic>cagL</italic> indicates that CagL‐dependent IL‐8 induction can occur independently of CagA translocation. In line with this notion, exogenous CagL complemented <italic>H. pylori</italic> Δ<italic>cagL</italic> 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 α<sub>5</sub>β<sub>1</sub>, 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.</p> </abstract>