A single-nucleotide polymorphism in a <i>Plasmodium berghei</i> ApiAP2 transcription factor alters the development of host immunity.

Akkaya, Munir; Bansal, Abhisheka; Sheehan, Patrick W; Pena, Mirna; Molina-Cruz, Alvaro; Orchard, Lindsey M; Cimperman, Clare K; Qi, Chen-Feng et al. · Sci Adv · 2020

basic_science · Level V

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Abstract

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite <i>Plasmodium berghei</i> (<i>Pb</i>) NK65 allowed infected mice to mount a T helper cell 1 (T<sub>H</sub>1)-type immune response that controlled subsequent infections. As compared to <i>Pb</i>NK65<sup>S</sup>, <i>Pb</i>NK65<sup>F</sup> parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. <i>Pb</i>NK65<sup>F</sup> infections resulted in an early interferon-γ response and a later expansion of germinal centers, resulting in high levels of infected red blood cell-specific T<sub>H</sub>1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies. Thus, the <i>Pb</i> ApiAP2 transcription factor functions as a critical parasite virulence factor in malaria infections.

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