IFNγ, TNFα polymorphisms and IFNγ serum levels are associated with the clearance of drug-resistant P. falciparum in Malian children
IFNγ, TNFα polymorphisms and IFNγ serum levels are associated with the clearance of drug-resistant P. falciparum in Malian children
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DOI：
10.1016/j.cyto.2023.156137
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发表时间：
2023-02-09
期刊：
影响因子：
3.8
通讯作者：
Djimde, Abdoulaye
中科院分区：
文献类型：
--
作者：
Kouriba, Bourema;Arama, Charles;Djimde, Abdoulaye
在疟疾流行的环境中，宿主免疫被认为可以清除抗药性寄生虫。然而，寄生虫清除所涉及的免疫遗传机制知之甚少。表征宿主的免疫力和参与控制寄生虫感染的基因可以为血液阶段疟疾疫苗的开发提供信息。本研究探讨宿主调节细胞因子和免疫基因组学因素与恶性疟原虫携带氯喹耐药genotype.Biological样本的清除先前的药物疗效试验在两个马里地方进行了检索。使用寄生虫DNA对恶性疟原虫氯喹抗性转运蛋白（Pfcrt）基因进行基因分型。携带突变等位基因（Pfcrt-76 T）寄生虫的儿童根据其清除寄生虫的能力进行分类。在血清中测量不同细胞因子的水平。使用人类DNA对疟疾易感性相关的人类特异性基因的多态性进行基因分型。Kolle的Pfcrt-76 T感染率显著高于Bandiagara（81.6%vs38.6%，p < 10-6），Bandiagara清除其突变寄生虫的儿童感染率显著高于Kolle（82.2%vs67.4%，p < 0.05）。宿主基因分型显示IFN-γ-874 T和TNF-α-308 A等位基因与寄生虫清除呈正相关。细胞因子分析显示IFN-γ水平与寄生虫清除呈正相关（p = 0.04）。本研究强调了宿主免疫和免疫遗传因素在清除抗性寄生虫中的作用，表明进一步表征这些多态性可能有助于开发抗寄生虫治疗策略的新方法。
Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood -stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype.Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA. The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6 % vs 38.6 %, p < 10-6).The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2 % vs 67.4 %, p < 0.05). The genotyping of host genes revealed that IFN-gamma -874 T and TNF-alpha -308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-gamma level was positively associated with parasite clearance (p = 0.04).This study highlights the role of host's immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these poly-morphisms may help to develop novel approaches to antiparasitic treatment strategies.