Nod1 signaling to extracellular mucosal bacteria in epithelial cells

The mechanisms by which epithelial cells discriminate between pathogenic and commensal micro-organisms are still poorly understood. Nod1 (CARD4), a cytosolic molecule with homology to plant resistance proteins, was shown to initiate innate immune signaling in epithelial cells to invasive bacterial pathogens. We recently identified Nod1 as also playing a key role in epithelial cell responses to a non-invasive bacterium, Helicobacter pylori. The Nod1 signaling cascade was triggered by H. pylori delivery of peptidoglycan, a component of its cell wall, to host cells. It appeared that Nod1 recognition of H. pylori might represent a novel paradigm of host innate immune “sensing” of non-invasive bacteria that cause mucosal inflammation. We have tested this hypothesis by investigating epithelial cell responses to intestinal Helicobacter spp., several of which are known to induce colitis in animal hosts. Of the various isolates tested, only one (Helicobacter muridarum) induced Nod1-dependent signaling in intestinal epithelial cells. H. muridarum is a member of the intestinal flora of conventional rodents, yet has previously been associated with the development of colitis in mice. Taken together, the findings suggest that Nod1 may play a key role in the etiology of a variety of inflammatory conditions triggered by the host microflora.