Credit: R. L. Ferrero, A. Cardona and C. Soubert

Helicobacter pylori, like many other pathogenic bacteria, inserts substances into human cells that can modify cell behavior. Jérôme Viala et al. now find that human cells have turned this system against the bacterium. Delivery of the bacterial substance peptidoglycan alerts the cell to the presence of H. pylori, setting in motion antibacterial defenses (Nature Immunology 5, 1166–1174). (Shown is H. pylori infecting human cells; peptidoglycan is in purple and individual bacteria appear as refractile objects).

The authors began with the question: how does the host recognize H. pylori? Previous researchers had ruled out some suspects, such as Toll-like receptors, which recognize conserved bacterial components (see p. 1175). The authors turned their attention to another set of proteins that recognize bacteria, the Nod proteins, and found that human cells needed Nod1 to mount an inflammatory response to H. pylori. There was one problem with this scenario, however: Nod proteins are expressed inside cells, and H. pylori is an extracelluar pathogen.

The type IV secretion system gets around this issue. The researchers provide evidence that the system delivers peptidoglycan, which Nod1 recognizes, into the cell. This recognition sets in motion an inflammatory response that can lead to tissue damage. The type IV secretion system is encoded on a region of bacterial DNA—the Cag pathogenicity island—which is present in H. pylori strains that tend to be associated with more severe forms gastric inflammation, ulceration and cancer.