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

INF I 型在轻度恶性疟原虫感染中的作用及其与 w 的关联

• 批准号: 8472812
• 负责人: Johanna Patricia Daily
• 金额: $ 24.97万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8472812
• 关键词: Address; Apoptosis; Carrier State; Child; Clinical; Country; Cross-Priming; Development; Disease; Disease Outcome; Disease model; Effector Cell; Goals; Human; Immune response; Immunology; Individual; Infection; Interferon Type I; Interferons; Intervention; Laboratories; Life; Longitudinal Studies; Malaria; Malawi; Mission; Morbidity - disease rate; Parents; Plasmodium falciparum; Risk; Role; Scientist; Symptoms; T-Lymphocyte; Training; Vaccines; Work; base; microbial; mortality; pathogen; programs; response; transmission process

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.

疟疾在全球范围内继续引起明显的发病率和死亡率。感染会导致严重 威胁生命的疾病，轻度症状或无症状的马车状态。防止严重 疾病结局自然发生在居民高质质质恶性疟原虫传播区域 该保护与反复暴露有关，导致轻度至无症状 在非免疫个体中发生的而不是毁灭性的并发症。基础 几十年前进行的临床观察中的特征仍然很差。我们的小组和其他人 在疟疾感染期间已经确定了IINF型反应的作用。 I型Inf被称为 强大的免疫调节分子可以促进激活，分化甚至凋亡 DCS的效应细胞（例如NK和T淋巴细胞AHD）的交叉促进。因此我们的工作 假设提出，疟疾感染中的I型IFN反应更强与 更具保护性的宿主先天和适应性免疫反应。我们将研究I型的作用 轻度疟疾期间的INF以及这种反应在重复感染期间是否发生变化 个人，改变重新感染的风险，并与传输强度有关。这个建议 带来Lauvau博士在研究针对微生物病原体的免疫反应方面的专业知识，博士 每日与马拉维ICEMR计划的转录分析方面的专业知识，以表征先天性 在一项纵向研究中，随后在患有轻度疾病的儿童的自适应免疫反应。 该建议将增强马拉维ICEMR的目标，以了解疟疾的决定因素 疾病。宿主免疫反应改变了疟疾疾病的发展，因此该提议 将进一步表征宿主反应以告知疾病模型。我们也会 解决如何通过疟疾控制干预措施的传播强度变化 研究可能会改变宿主反应和疾病表现。最后，该提议将进一步 马拉维ICEMR培训马拉维科学家并建立国内的培训任务 疟疾免疫学的实验室和科学能力。