IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND COMPROMISED POPULATIONS

儿童、老年人和受损人群的免疫功能和生物防御

• 批准号: 8358069
• 负责人: PETER J DIDIER
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358069
• 关键词: Adult; Age; Animals; Behavior; CD3 Antigens; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Child; Culicidae; Desire for food; Elderly; Encephalitis; Fever; Funding; Grant; Immune response; Immunologic Deficiency Syndromes; Individual; Infection; Life; Macaca fascicularis; Macaca mulatta; National Center for Research Resources; Peripheral Blood Mononuclear Cell; Population; Primates; Principal Investigator; Publishing; Research; Research Infrastructure; Resources; Risk; Salivary Glands; Source; T-Cell Depletion; T-Cell Proliferation; Testing; Thymectomy; United States National Institutes of Health; Viremia; Virus; Virus Diseases; West Nile virus; Whole Blood; adaptive immunity; biodefense; cost; eosinophil; immune function; monocyte; mortality; nonhuman primate; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Individuals suffering neuroinvasive illness have mortality rates of less than 4% if under the age of 70, after which rates rise to over 20%. Our collaborators at ONPRC challenged sixteen age rhesus macagues (17-30 yrs) and 9 adult Rhesus (6-9 yrs) with two does of virus (1 x 107 or 1 x 109 pfu/animal); some experiments included mosquito salivary gland extract (SGE) generated from the insectory at TNPRC. Additionally fifteen Cynomolgus monkeys were challenged after thymectomy and/or CD8 T cell depletion to test various levels of immunodeficiency. Animals remained clinically normal. No fever, change in appetite, or behavior was detected that could be attributed to WNV infection. Quantitative PCR of whole blood revealed discrete and short lived viremia; however infectious virus was never isolated. Analysis of innate immune response revealed a marked increase in monocytes and eosinophils (with SGE) between days 2 and 10 post infection. Additionally flow cytometric analysis of PBMC revealed increased proliferation of CD3- cells. With regard to adaptive immunity, an age-associated reduction in CD4+ T cell proliferation was found. Humoral responses developed and were detected in nearly all animals. The results suggest that non-human primates mount and maintain an effective innate defense to WNV challenge. This project ended in June, 2010 and results were published in December.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 西尼罗河病毒（WNV）感染脑炎的风险随着年龄的增长而急剧增加。患有神经侵入性疾病的人在70岁以下的死亡率低于4%，之后死亡率上升到20%以上。我们在ONPRC的合作者用两种剂量的病毒（1 × 107或1 × 109 pfu/动物）攻击16只年龄恒河猴（17-30岁）和9只成年恒河猴（6-9岁）;一些实验包括从TNPRC的昆虫库中产生的蚊子唾液腺提取物（SGE）。此外，在胸腺切除术和/或CD 8 T细胞耗竭后，对15只食蟹猴进行激发，以测试各种水平的免疫缺陷。动物临床表现正常。没有发现可归因于西尼罗河病毒感染的发热、食欲改变或行为改变。全血的定量PCR显示离散和短暂的病毒血症;然而，从未分离出感染性病毒。先天性免疫应答的分析揭示了在感染后第2天和第10天之间单核细胞和嗜酸性粒细胞（具有SGE）的显著增加。此外，PBMC的流式细胞术分析显示CD 3-细胞的增殖增加。在获得性免疫方面，发现了与年龄相关的CD 4 + T细胞增殖的减少。几乎所有动物都出现并检测到了体液应答。结果表明，非人灵长类动物对西尼罗河病毒的攻击建立并保持有效的先天防御。 该项目于2010年6月结束，结果于12月公布。