The innate immune molecule, NOD1, regulates host defence responses to infection by Gram-negative pathogens. These responses are initiated by NOD1 sensing of soluble fragments of cell wall peptidoglycan (muropeptides). We previously showed that virulent strains of the gastric pathogen, Helicobacter pylori, deliver these muropeptides to cytosolic NOD1 via the actions of a type IV secretion system (T4SS). NOD1 activation triggers a downstream signalling cascade, characterised by induction of NF-ĸB-dependent pro-inflammatory and immune responses, resulting in the production of soluble immune-mediators e. g. chemokines, cytokines and antimicrobial peptides. Consistent with known role of NOD1 in host defence functions, we showed that Nod1-/- mice which had been challenged with H. pylori bacteria harbouring a functional T4SS, exhibited higher bacterial loads than wild-type animals, at days 7 and 30 post-challenge. Subsequent studies, however, revealed a counter-intuitive observation that H. pylori bacteria are able to modify their peptidoglycan composition so as to ensure enhanced NOD1 signalling in vivo. This suggested that H. pylori may be able to subvert the NOD1 pathway for its own benefit. Using a transcriptome approach, we identified a novel group of NOD1-regulated genes, encoding products with roles in anti-apoptotic, cell survival and pro-proliferative functions. Several of these factors have previously been linked to gastric carcinogenesis. We hypothesise that H. pylori exploits the NOD1 signalling pathway to induce cell survival responses that favour bacterial persistence in the stomach. In agreement with this hypothesis, preliminary experiments have shown that Nod1-/- mice with chronic H. pylori infection (i. e. 2 months post-challenge) display significantly reduced bacterial loads, when compared with wild-type animals. We propose that H. pylori activation of the NOD1 signalling represents a “double-edged sword”, whereby changes in peptidoglycan composition favouring bacterial persistence may also promote gastric carcinogenesis in certain hosts.