Role of type INF I during mild Plasmodium falciparum infection and association w

疟疾继续在全世界造成显着的发病率和死亡率。感染可导致严重的 危及生命的疾病、轻微的症状或无症状的携带状态。保护免受严重 疾病结局自然发生在恶性疟原虫高传播区 这种保护与反复接触疟疾有关，导致轻微或无症状。 而不是发生在非免疫个体中的破坏性并发症。其基础是 几十年前的这一临床观察结果的特征仍然很差。我们的团队和其他人 已经确定了IINF类型反应在疟疾感染过程中的作用。第一类干扰素称为 强大的免疫调节分子，可促进活化、分化甚至凋亡 NK、T淋巴细胞等效应细胞的表达更倾向于DC的交叉激发。因此我们的工作 假说认为，疟疾感染中较强的I型干扰素反应与 更具保护性的宿主先天和适应性免疫反应。我们将研究类型I的作用 轻度疟疾期间的INF以及在一次重复感染期间这种反应是否改变 个体感染会改变再次感染的风险，并与传播强度有关。这项建议 带来了劳沃博士在研究对微生物病原体的免疫反应方面的专业知识。 Daily在马拉维ICEMR计划转录分析方面的专业知识 以及随后在一项纵向研究中对轻度疾病儿童的适应性免疫反应。 这项提案将加强马拉维国际经济、经济和环境研究中心关于了解疟疾决定因素的目标。 疾病。宿主免疫反应改变了疟疾的发展，因此这一建议 将提供宿主反应的进一步特征，为疾病模型提供信息。我们还将 解决如何通过在父母中进行疟疾控制干预来改变传播强度 研究可能会改变宿主的反应和疾病表现。最后，这项提议将进一步推动 马拉维ICEMR的培训任务，通过培训马拉维科学家和在国内建立 疟疾免疫学的实验室和科学能力。

Malaria continues to cause marked morbidity and mortality worldwide. Infection can result in severe life threatening disease, mild symptoms or an asymptomatic carriage state. Protection from severe disease outcomes naturally occurs in residents high Plasmodium falciparum transmission regions This protection is related to repeated malaria exposures which result in mild to asymptomatic carriage rather than devastating complications which occurs in non-immune individuals. The basis of this clinical observation made decades ago remains poorly characterized. Our group and others have identified a role for type IINF response during malarial infection. Type I INF is known as a powerful immunomodulatory molecule that can promote activation, differentiation or even apoptosis of effector cells such as NK and T lymphocytes ahd favor cross-priming by DCs. Thus our working hypothesis proposes that a stronger type I IFN response in malaria infections is associated with a more protective host innate and adaptive immune responses. We will examine the role of type I INF during mild malaria and whether this response changes during repeated infections in one individual, alters the risk of re-infection and is associated with transmission intensity. This proposal brings Dr. Lauvau's expertise in studying immune responses against microbial pathogens, Dr. Daily's expertise in transcriptional analysis with the Malawi ICEMR program to characterize innate and subsequent adaptive immune responses in children with mild disease in a longitudinal study. This proposal will enhance the Malawi ICEMR goals of understanding the determinants of malarial disease. Host immune responses alter the development of malarial disease and thus this proposal will provide a further characterization of host responses to inform disease models. We will also address how changes in transmission intensity through malaria control interventions in the parent study may alter host response and disease presentation. Finally this proposal will further the training mission of the Malawi ICEMR by training Malawian scientists and building in-country laboratory and scientific capacity in malaria immunology.