The role of rosetting in the multiplication of Plasmodium falciparum: rosette formation neither enhances nor targets parasite invasion into uninfected red cells.

The effect of rosette formation on the multiplication in vitro of Plasmodium falciparum was studied in order to establish whether rosetting acts as a major virulence factor in the pathogenesis of severe malaria by facilitating invasion of uninfected red cells. Invasion rates for rosetting (R+) and non-rosetting (R-) parasites selected from the same clone, PA1, of P. falciparum were similar over a range of starting parasite concentrations when assayed in both static cultures and conditions of shear stress comparable with microvascular flow. However, incubation of both R+ and R- parasites under simulated conditions of flow led to decreased invasion and fewer multiply-infected red cells as we have previously observed. Studies using fluorescently labelled red cells or reticulocytes demonstrated that rosetting did not alter the rates of invasion or target merozoites into the uninfected cells comprising a rosette. Preferential invasion of reticulocytes occurred regardless of rosetting or conditions of flow. Although the role of rosetting in the pathogenesis of malaria might relate to microvascular obstruction or perhaps the restriction of phagocytosis, our data suggest that rosetting does not play a role in the invasion or targeting of parasites into uninfected cells, eliminating this mechanism to explain the association of virulence with the rosetting parasite phenotype.