Helicobacter pylori utilizes DNA shuffling to modulate the gastric inflammatory response

Infections with the human gastric pathogen Helicobacter pylori are among the most common infections worldwide, causing a significant burden of disease due to their association with gastric carcinogenesis. A hallmark of acute and chronic H. pylori infection is intense inflammation in the gastric submucosa, which is strongly enhanced by the activity of a major bacterial virulence factor, the cytotoxin-associated gene (Cag)-type IV secretion system (T4SS). Despite intense research in recent years, the molecular mechanisms leading to proinflammatory signaling by the Cag-T4SS are only partly understood. Barrozo et al. now show that this proinflammatory capability of H. pylori can be reduced or increased in vivo by recombination events in a particular repeat region of the T4SS component CagY, and that lymphocytes are the main driving force triggering such events. The results highlight the mutual interplay between a major bacterial virulence factor and the immune system and might aid in understanding bacterial persistence.