Variation in Human Innate Immunity

人类先天免疫的变异

• 批准号: 7638366
• 负责人: Thomas R Martin
• 金额: $ 88.93万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7638366
• 关键词: Adult Respiratory Distress Syndrome; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic-resistant organism; Bacteria; Biological Products; CD14 gene; Candidate Disease Gene; Categories; Centers for Disease Control and Prevention (U.S.); Chronic; Disease; Disease Outbreaks; Dizygotic Twins; Event; Exposure to; Gene Expression; Genes; Genetic; Genetic Polymorphism; Goals; Haplotypes; Heating; Human; IRAK4 gene; Immune; Immune response; In Vitro; Individual; Inflammatory; Inflammatory Response; Inherited; Integration Host Factors; Leukocytes; Lung; Lung diseases; Malaria; Measures; Mechanical ventilation; Meningococcal Infections; Molecular; Molecular Profiling; Monozygotic Twinning; Monozygotic twins; Natural Immunity; Nucleotides; Organism; Outcome; Pathway interactions; Patients; Pattern; Persons; Population; Population Distributions; Predisposition; Preventive; Production; Resource Allocation; Resources; Risk; Sepsis; TLR2 gene; TLR4 gene; TOLLIP gene; Twin Studies; Variant; Whole Blood; Yersinia pestis; aerosolized; concept; cytokine; genetic linkage analysis; human IRAK4 protein; human TOLLIP protein; in vitro Model; killings; mortality; novel; novel therapeutics; pathogen; response; therapeutic target

This project focuses on identifying the factors that determine human susceptibility to bioweapons agents. This is an imPortant goal, as we need to be able to identify high-risk groups in order to target effective preventive measures. Evidence from human and animal studies supports the concept that host factors, some of which are genetically determined, are important modifiers of susceptibility to diseases such as malaria and meningococcal infection. There is considerable evidence demonstrating person to person variability in innate immune inflammatory responses to bacterial products. This variability is likely to extend to innate immune inflammatory responses to products of bacteria that may be used as bioweapons agents and could influence outcomes after exposure to such agents. An understanding of the molecular mechanisms underlying human variability in innate immune inflammatory responses to these agents may help to prospectively identify populations at high-risk for poor outcomes after a bioweapons attack. This would aid in the optimal allocation of resources and may identify new therapeutic targets. We propose to measure the variability in innate immune responses to Y. pestis and other potential bioweapons agents using an in vitro model of whole blood responses to bacterial products. We will investigate the magnitude of the genetic component of this variability through a classical twins study. We will determine the extent to which specific allelic haplotypes contribute to this variability. Finally, we will identify innate immune response profiles in patients with chronic respiratory diseases, a population that is likely to be at high-risk for poor outcomes in the event of exposure to aerosolized Y. pestis and other bioweapons agents. Our initial emphasis will be on Y. pestis, but the approaches developed in these studies will be adapted to subsequent studies of other potential bioweapons agents.

这个项目的重点是确定决定人类对生物武器易感性的因素