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.

疟疾继续在全世界造成显著的发病率和死亡率。感染可导致严重的 危及生命的疾病、轻微症状或无症状的携带状态。保护免受严重 恶性疟原虫高传播地区的居民自然会出现疾病结局 这种保护与反复接触疟疾有关， 而不是发生在非免疫个体中的毁灭性并发症。基础 几十年前的临床观察仍然没有得到充分的表征。我们集团和其他 已经确定了IINF型反应在疟疾感染中的作用。I型INF被称为 强大免疫调节分子，可促进活化、分化甚至凋亡 NK细胞和T淋巴细胞等效应细胞的激活有利于DC的交叉致敏。我们的工作 一种假说认为，在疟疾感染中，I型干扰素反应较强与 保护宿主的先天性和适应性免疫反应。我们将研究I型的作用 INF在轻度疟疾期间以及这种反应是否在一次重复感染期间发生变化。 个体，改变了再感染的风险，并与传播强度有关。这项建议 带来了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， Daily在马拉维ICEMR项目转录分析方面的专业知识， 和随后的适应性免疫反应在轻度疾病的儿童在纵向研究。 这一建议将加强马拉维ICEMR了解疟疾决定因素的目标， 疾病宿主免疫反应改变疟疾疾病的发展，因此该提议 将提供宿主反应的进一步表征，以告知疾病模型。我们还将 通过父母的疟疾控制干预措施解决传播强度的变化 研究可能改变宿主反应和疾病表现。最后，这一建议将进一步促进 通过培训马拉维科学家和在国内建立 在疟疾免疫学方面的实验室和科学能力。