Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Sci Adv. 2020 Feb 5;6(6):eaaw6957. doi: 10.1126/sciadv.aaw6957. eCollection 2020 Feb.
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 () NK65 allowed infected mice to mount a T helper cell 1 (T1)-type immune response that controlled subsequent infections. As compared to NK65, NK65 parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. NK65 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 T1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies. Thus, the ApiAP2 transcription factor functions as a critical parasite virulence factor in malaria infections.
疟疾免疫力的获得既非常缓慢又不可预测。目前，我们对影响宿主产生保护性免疫反应能力的疟原虫基因知之甚少。在这里，我们表明，啮齿动物疟原虫 （） NK65 中的一个 ApiAP2 转录因子中的单核苷酸多态性（SNP）导致单个氨基酸改变（S 到 F），使感染的小鼠能够产生 T 辅助细胞 1（T1）-型免疫反应，从而控制随后的感染。与 NK65 相比，NK65 寄生虫差异表达了 46 个基因，其中大多数被预测在免疫逃避中发挥作用。NK65 感染导致早期干扰素-γ反应和随后生发中心的扩张，导致高水平的感染红细胞特异性 T1 型免疫球蛋白 G2b（IgG2b）和 IgG2c 抗体。因此，ApiAP2 转录因子在疟疾感染中作为寄生虫毒力因子发挥关键作用。
