Data and analysis scripts for manuscript "Elevated Plasmodium falciparum sexual conversion in HbAC and HbAS red blood cells in naturally infected malaria patients"

Dataset and scripts for manuscript on sexual conversion assays. Abstract: Malaria transmission relies on the differentiation of asexual parasites into gametocytes, a process initiated by sexual conversion (SC). Mutations in the host hemoglobin beta (HBB) gene are known to influence parasite growth and disease outcome, yet their impact on SC remains unclear. We investigated the effect of HBB mutant genotypes on Plasmodium falciparum SC and humoral immunity in individuals from Nanoro, Burkina Faso. To measure SC rates in natural human malaria infections, we developed a new ex vivo SC assay (evSCA). We found that in human natural P. falciparum infections, SC rates were higher in individuals with HbAS or HbAC than in individuals with wild-type HBB (HbAA). Consistently, using an in vitro SC assay (ivSCA) based on the NF54-gexp02-Tom reporter line we found that cultures grown in HbAS red blood cells (RBCs) had higher SC rates than those grown in HbAA RBCs. Furthermore, IgG and IgM responses against trophozoite- and stage I gametocyte-infected RBC antigens, quantified by flow cytometry, did not differ between plasma from individuals with different HBB genotypes. These results demonstrate that exposure to RBCs with HBB mutations enhances SC, highlighting a host-genetic factor that may influence malaria transmission potential.用于性转化试验相关研究手稿的数据集及配套脚本。 摘要： 疟疾传播依赖于无性期疟原虫向配子体的分化，该过程由性转化（sexual conversion, SC）启动。已知宿主血红蛋白β（hemoglobin beta, HBB）基因的突变可影响疟原虫生长与疾病转归，但此类突变对性转化的影响仍不明晰。本研究针对布基纳法索纳诺罗地区的人群，探究了HBB突变基因型对恶性疟原虫（Plasmodium falciparum）性转化及体液免疫的影响。为量化自然人体疟疾感染中的性转化速率，我们开发了一种新型离体性转化试验（ex vivo SC assay, evSCA）。研究发现，在自然发生的恶性疟原虫感染中，携带HbAS或HbAC基因型的个体其性转化速率高于携带野生型HBB（HbAA）的个体。基于NF54-gexp02-Tom报告细胞系构建的体外性转化试验（in vitro SC assay, ivSCA）得到了一致结果：在HbAS型红细胞（red blood cells, RBCs）中培养的疟原虫，其性转化速率高于HbAA型红细胞培养的疟原虫。此外，通过流式细胞术（flow cytometry）定量检测的针对滋养体及I期配子体感染红细胞抗原的IgG与IgM应答水平，在不同HBB基因型个体的血浆中无显著差异。本研究结果表明，暴露于携带HBB突变的红细胞可增强疟原虫的性转化过程，这揭示了一个可影响疟疾传播潜能的宿主遗传因素。