A cell biologist's view of host cell recognition and invasion by malarial parasites

Abstract

The migration of various Apicomplexan parasites through host cells and tissues is examined. Two approaches are taken. First a comparative examination of the invasive stages from an ultrastructural and biochemical viewpoint. Second a critical review of the mechanism of recognition and invasion of host cells. The ultrastructural organization of the invasive stages is highly conserved and invariably includes three classes of organelle whose probable functions can be deduced. These organelle classes are: (i) The rhoptry/microneme/osmiophilic body/microsphere complex. These electron-dense, membrane-limited organelles are situated close to the parasite plasmalemma, and are often concentrated or specifically localized within the apical complex. Their contents are probably secreted by the parasite and induce various modifications in the host cell plasmalemma. However, it is concluded that the exact role of these organelles has not yet been determined nor their mechanism of action adequately evaluated. (ii) The microtubule cytoskeleton and associated structures (e.g., apical rings and conoid, etc.). These are structural organelles, and the microtubules probably direct the locomotion of the parasites. Locomotion is possibly achieved by a directed capping reaction, (iii) The plasmalemma and inner membrane vacuoles. The plasmalemma has a glycocalyx of varying complexity which includes molecules capable of host cell recognition and binding. It is speculated that host cell invasion is achieved by the directed capping of these molecules. Whilst appreciating the very specific nature of host cell recognition and invasion in some parasite stages (e.g., RBC invasion by the malarial merozoite), a marked contrast is observed in the ability of other stages of the malarial life-cycle (sporozoite and ookinete) to invade, migrate through, and escape from varied types of host cell. The latter breadth of ability is even more evident in other members of the phylum. Questions are therefore raised on the relevance of specific recognition of host cell membranes in all cases of trans-membrane migration. It is speculated that receptors are required for the induction of a parasitophorous vacuole (and thus host cell survival), whereas receptors are of little relevance when the membrane and host cell are directly ruptured e.g., during escape from the previously parasitized host cell (in which case survival of the host cell is unimportant).