Polymorphisms in the Fc Gamma Receptor IIIA and Toll-Like Receptor 9 Are Associated with Protection against Severe Malarial Anemia and Changes in Circulating...

Abstract

An understanding of the immunogenetic basis of naturally acquired immunity to Plasmodium falciparum infection would aid in the designing of a rationally based malaria vaccine. Variants within the Fc gamma receptors (FcγRs) mediate immunity through engagement of immunoglobulin G and other immune mediators, such as gamma interferon (IFN-γ), resulting in erythrophagocytosis and production of inflammatory cytokines in severe malarial anemia (SMA). The Toll-like receptors (TLRs) trigger transcription of proinflammatory cytokines and induce adaptive immune responses. Therefore, these receptors may condition malaria disease pathogenesis through alteration in adaptive and innate immune responses. To further delineate the impacts of FcγRIIIA and TLR9 in SMA pathogenesis, the associations between FcγRIIIA− 176F/V and TLR9− 1237T/C variants, SMA (hemoglobin [Hb]< 6.0 g/dl …