THE ROLE OF RESETTING 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 Plas modium falciparum was studied in order to establish whether resetting acts as a major virulence factor in the pathogenesis of severe malaria by facilitating invasion of uninfected red cells, Invasion rates for resetting (R+) and non-resetting (R-) parasites selected from the same clone, PA1, of P. falciparum were similar over a range of starting pa rasite concentrations when assayed in both static cultures and conditi ons of shear stress comparable with microvascular flow However, incuba tion of both R+ and R- parasites under simulated conditions of flow le d to decreased invasion and fewer multiply-infected red cells as we ha ve previously observed. Studies using fluorescently labelled red cells or reticulocytes demonstrated that resetting did not alter the rates of invasion or target merozoites into the uninfected cells comprising a rosette. Preferential invasion of reticulocytes occurred regardless of resetting or conditions of now Although the role of resetting in th e pathogenesis of malaria might relate to microvascular obstruction or perhaps the restriction of phagocytosis, our data suggest that resett ing does not play a role in the invasion or targeting of parasites int o uninfected cells, eliminating this mechanism to explain the associat ion of virulence with the resetting parasite phenotype.