Dendritic cells (green) reach their finger-like protrusions past the gut epithelia to catch bacteria.

Dendritic cells (DCs) stretch finger-like extensions into the gut to capture bacteria. But, according to Chieppa et al. (page 2841), it is the gut epithelial cells that first recognize the bacteria and then give DCs the tip-off.

Regular sampling of gut bacterial antigens by the immune system is necessary for maintaining tolerance to commensal bacteria and for defending against pathogens. DCs gather bacterial antigens using their extensions, but Chieppa et al. show that these extensions are not a constitutive feature of gut DCs.

Treatment of mice with antibiotics reduced the number of DC extensions in the small bowel, whereas oral infection of mice with Salmonella increased their numbers. DC extensions are thus dependent on the presence of the bacteria themselves. Indeed, live imaging using intravital microscopy showed that DC extensions begin to emerge from the gut wall following bacterial exposure and remain protruded for 10–40 min before retracting with their quarry.

Recognition of bacteria by innate immune cells is often dependent on Toll-like receptors (TLRs). Recent studies reveal that gut epithelial cells also have TLRs, and the group show here that mice lacking specific epithelial but not DC TLRs failed to extend DC processes across their gut wall in response to the relevant bacterial stimuli. Although the team does not yet know how epithelial cells alert the DCs, the gut barrier function of the epithelial cells makes them the perfect choice to be the first to perform identity checks on gut bacteria.