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

作者：Gorrell Rebecca J; Guan Jyeswei; Xin Yue; Tafreshi Mona Anoushiravani; Hutton Melanie L; McGuckin Michael A; Ferrero Richard L; Kwok Terry^*

来源：Cellular Microbiology, 2013, 15(4): 554-570.

DOI：10.1111/cmi.12055

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 51 integrin and the arginineglycineaspartate (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 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 cagL mutant in activating NF-B and inducing IL-8 without restoring CagA translocation. The CagA translocation-independent, CagL-dependent IL-8induction involved host signalling via integrin 51, Src kinase, the mitogen-activated protein kinase (MAPK) pathway and NF-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.

• 出版日期2013-4
• 单位河北医科大学