Figure 5.

Conceptual model of the interaction of H. pylori with lactoferrin. H. pylori infection of the gastric niche results in production of lactoferrin. Apo-lactoferrin lacks iron and, therefore, cannot be utilized as a source of nutrient iron under iron-limited conditions, resulting in the elaboration of the cag T4SS at the host interface. The H. pylori cag T4SS translocates proinflammatory substrates, including the oncogenic CagA cytotoxin, into host gastric epithelial cells. As a consequence of the activity of the H. pylori cag T4SS, host cells upregulate production of the proinflammatory cytokine and chemokine interleukin 8 (IL-8). Holo-lactoferrin can be utilized as a source of nutrient iron for H. pylori in conditions where iron availability is low. Holo-lactoferrin represses the elaboration of the H. pylori cag T4SS and represses the proinflammatory activity of this toxin secretion system, resulting in decreased IL-8 secretion by host cells.