Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status

Following reports that a VacA(+)cag(+) toxigenic but not a VacA(-)cag(-) non-toxigenic Helicobacter pylori strain induced homotypic phagosome fusion in murine macrophages, we addressed that phenomenon in human cells. Mononuclear phagocytes and epitheloid cells were challenged with H. pylori strains of different vacA and cag genotypes and with VacA(-) and Cag(-) isogenic mutants, and chased in the absence or presence of signal transduction modulators. Electron microscopy revealed that, in monocytes: (i) homotypic phagosome fusion was frequently induced by all live H. pylori strains investigated but not by exogenous VacA; (ii) phagosomes containing bacteria fused, but not those containing latex beads; (iii) fusion resulted in communal compartments resembling giant multivesicular bodies; and (iv) formation of these compartments was blocked by inhibiting the host cell regulators PI 3-kinase, phospholipase C and p42 MAP kinase. Whereas some internalized bacteria remained viable 1 h after uptake, none survived a 24 h period. In contrast to monocytes, infected epitheloid cells rarely developed communal compartments. In combination, these results demonstrate that, in human monocytes, the H. pylori-induced homotypic phagosome fusion depends on neither the vacuolating cytotoxin VacA nor the cag pathogenicity island of H. pylori and does not result in prolonged intracellular survival.