Open AccessA novel NOD1 ‐ and CagA ‐independent pathway of interleukin‐8 induction mediated by the H elicobacter pylori type IV secretion system
Author(s) -
Gorrell Rebecca J.,
Guan Jyeswei,
Xin Yue,
Tafreshi Mona Anoushiravani,
Hutton Melanie L.,
McGuckin Michael A.,
Ferrero Richard L.,
Kwok Terry
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12055
Subject(s) - caga , nod1 , secretion , biology , microbiology and biotechnology , helicobacter pylori , integrin , mutant , immune system , nod2 , immunology , gene , innate immune system , biochemistry , genetics , receptor , virulence
Summary The type IV secretion system ( T4SS ) of H elicobacter 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 α 5 β 1 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 Δ virD4 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 Δ cagL mutant in activating NF ‐κ B and inducing IL ‐8 without restoring CagA translocation. The CagA translocation‐independent, CagL ‐dependent IL ‐8induction involved host signalling via integrin α 5 β 1 , Src kinase, the mitogen‐activated protein kinase ( MAPK ) pathway and NF ‐κ B 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.