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Why the Sickle Cell Disease Provides Resistance Against Malaria

Why the Sickle Cell Disease Provides Resistance Against Malaria

In this section, the reason why having one mutated copy of the sickle-cell gene confers resistance against malaria (specifically, malaria caused by P. falciparum) will be explored.

To begin, the typical way that the malaria pathogen affects cells will be discussed. In healthy red cells, clusters of extremely short pieces of actin filament located beneath the cell’s outer membrane serve to maintain the red cells’ flexible structure that allows them to move through miniscule passages and vessels. The malaria parasite tends to hijack these pieces of filament, remodeling them as an intracellular “bridges” to transport parasite-encoded proteins, called adhesin, to the cell surface. Adhesin is a crucial virulence factor that makes infected red cells “sticky,” causing the cells to glue to not only other cells, but also vessel walls. This leads to the microvascular inflammations throughout the body that is characteristic of malaria.

In a study conducted by Marek Cyrklaff et al., it was revealed that sickle cells restricted the hijacking and remodeling of actin filaments—a crucial step to the virulence of P. falciparum malaria. Red blood cells containing the sickle-mutated hemoglobin demonstrated several abnormalities that allowed for this restriction, including a dysfunctional cytoskeleton and an “out-of-reach” actin filament. Moreover, the host vesicles that are normally used by the parasite to transport adhesin and other parasite-encoded proteins to the cell surface end up floating in the extracellular space, because of the aberrant structure of the sickle cells. As a result of these changes, Cyrklaff speculated that erythrocytes affected by the mild, though common form of sickle cell disease, Hb SC, tend to confer a degree of resistance against malaria—the extent of and the ways to measure that degree are still unknown, however.