Helicobacter pylori interferes with leukocyte migration via the outer membrane protein HopQ and via CagA translocation.

The human gastric pathogen Helicobacter pylori is a paradigm for chronic bacterial infections. Persistent colonization of the stomach mucosa is facilitated by several mechanisms of immune evasion and immune modulation, such as avoidance of Toll-like receptor recognition or skewing of effector T cell responses. Interactions of H. pylori with different immune cells have been described with respect to immune cell activation, cytokine release, or oxidative burst induction. We show here that H. pylori infection of human granulocytes, or of HL-60 cells differentiated to a granulocyte-like phenotype (dHL-60 cells) results in inhibition of cell migration under different conditions. Migration of dHL-60 cells in a three-dimensional collagen gel was found to be inhibited independently of the cag pathogenicity island, whereas migration inhibition in an under agarose assay was dependent on the cag pathogenicity island, on its effector protein CagA, and on the outer membrane protein HopQ. CagA translocation into leukocytes is accompanied by its tyrosine phosphorylation and by proteolytic processing into an N-terminal 100 kDa and a C-terminal 35 kDa fragment at a distinct cleavage site. By using complemented H. pylori strains producing either phosphorylation-resistant or cleavage-resistant CagA variants, we show that CagA tyrosine phosphorylation is required for migration inhibition, but CagA processing is not. Our results suggest that direct contact of H. pylori with immune cells subverts not only their activation characteristics, but also their migratory behaviour.