This group also reported that H. pylori induced the anti-microbial peptide human β-defensin 2 in epithelial AGS cells, and this appeared to be mediated by NOD1-dependent activation of NF-kB [16]. This host cell response was reported to be cagPAI-dependent but OMV-mediated triggering of NOD1, which seemed to be less efficient than the cagPAI-dependent pathway, was not tested. Because whole bacteria, H. pylori lysates and OMVs, contain multiple possible PRR ligands, Watanabe et al. [17] used a more specifically defined Opaganib in vivo NOD1 ligand, namely γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), for

determining the ability of NOD1 ligands to trigger NF-κB activation. In epithelial cells, iE-DAP-activated NOD1 was not linked to NF-κB activation but to IRF7 stimulation resulting from RICK-binding to TNF receptor-associated factor TRAF-3. IRF7-induced type I interferon-β (IFN-β). The latter triggered an autocrine/paracrine loop that led to the synthesis of chemokines such as CXCL10, IL-8, and i-TAC [17]. Interruption of this loop in a mouse model increased bacterial load early after infection, indicating that such NOD1 emanating signals trigger anti-bacterial effector functions in mice. To reconcile the divergent findings with regard to NOD1-mediated NF-κB activation in H. pylori infection, it will be necessary to refine analyses whether (and how) NOD1 activation and NF-κB signaling are linked.

This may extend to the newly reported H. pylori NOD1 association with the MAPK and AP-1 signaling cascades [18]. Obviously, H. pylori can be sensed by members of all PRR families. Furthermore, Gringhuis et al. [19] showed that certain H. pylori strains selleck chemicals llc can, dependent on carbohydrate expression on their surfaces, negatively influence IL-6 Beta adrenergic receptor kinase and IL-12 secretion, but positively influence IL-10 secretion via binding to the dendritic cell-specific C-type lectin DC-SIGN. Despite the obvious challenges of weighing the relative contribution of these recognition processes, understanding the cell biology basis, e.g. of intracytoplasmic recognition of bacterial ligands, may hold interesting surprises.

Necchi et al. mapped the intracellular distribution of NOD-1 in histologic sections of infected patients and also in cells exposed to H. pylori in vitro, revealing so-called Particle-rich Cytoplasmic Structures (PaCS) [20]. These structures may be a kind of “aggresome” structures that are known to be linked to intracellular protein degradation [21]. Indeed they found NOD1 to be co-localized with H. pylori remnants (defined antigens such as VacA and outer membrane proteins) and with ubiquinated proteins and proteasomes. Furthermore, this study highlights another level of complexity in host–H. pylori interplay, i.e. the impact of the pathogen’s subcellular distribution. Our current knowledge of the subcellular localization of H. pylori and the existence of differential localization between strains remains minimal.