Host Endothelial Response to TNF in Cerebral Malaria: Variations & Heritability

恶性疟疾是发病率和死亡率的主要原因，决定疟疾的因素 单纯疟疾(UM)与脑型疟疾(CM)的发展还不完全清楚。很有可能， 然而，许多不同宿主、寄生虫、媒介和环境因素结合在一起决定了 每种疟疾的严重程度。我们发现，肿瘤坏死因子反应性的异质性确实出现在 血管内皮细胞水平，一种可能影响患者病情严重程度的多样性 得了疟疾。这个项目的主要目标是破译不同的分子机制 血管内皮细胞对肿瘤坏死因子反应的个体间差异，以开发工具来识别患者 风险，并开发新的治疗方法。 为此，我们将对我们所描述的对肿瘤坏死因子的反应性差异进行广泛的分析 在UM(低应答者)和CM(高应答者)患者之间，使用从患者身上新分离的细胞 在印度鲁尔克拉的伊斯帕特综合医院住院。我们将分析这种变化，并评估它是否 由于参数是

Plasmodium falciparum malaria is a major cause of morbidity and mortality and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. It is likely, however, that many different host, parasite, vectorial and circumstantial factors combine to determine the severity of each malarial illness. We showed that heterogeneity in TNF responsiveness does occur at the level of the vascular endothelial cell, a diversity that might influence the severity of the disease in patients with malaria. The main objective of this project is to decipher the different molecular mechanisms underlying the endothelial inter-individual variations in response to TNF in order to develop tools to identify patients at risks and develop new therapeutic approaches. For this, we will carry out an extensive analysis of the difference in responsiveness to TNF we described between UM (low responders) and CM (high responders) patients, using cells freshly isolated from patients admitted at Ispat General Hospital in Rourkela, India. We will analyze this variation and assess whether it is due to parameters that are