MELIODOSIS

鼻根疽

基本信息

批准号：
7958676
负责人：
CHAD J. ROY
金额：
$ 5.8万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7958676
关键词：
Acute Animal Model Animals Area Australia Biological Biological Products Breathing Bronchopneumonia Burkholderia Burkholderia pseudomallei Cavia Cells Centers for Disease Control and Prevention (U.S.)Chronic Clinical Communicable Diseases Computer Retrieval of Information on Scientific Projects Database Disease Disease model Dose Emerging Communicable Diseases Exposure to Funding Goals Grant Hamsters Immune Immune response Inbred BALB C Mice Incidence Infection Institution Investigation Laboratories Lung Mediating Melioidosis Modeling Mouse Strains Pathogenesis Pathology Play Predisposition Primates Research Research Personnel Resources Rodent Diseases Role Route Sepsis Source Southeastern Asia Syndrome Transgenic Organisms United States National Institutes of Health aerosolized cytokine in vivo nonhuman primate response subcutaneous

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Melioidosis is an infectious disease caused by exposure to Burkholderia pseudomallei, a saprophyte found primarily in Southeast Asia and Northern Australia. Melioidosis is considered an emerging infectious disease and epizoonotic agent. Incidence of B. pseudomallei-associated bacterial sepsis and bronchopneumonia has significantly increased in endemic areas over the past decade. B. pseudomallei is a biological threat agent primarily because of its remarkable infectivity at a low (less than 100 bacterial cells) dose. As a result, the Centers of Disease Control and Prevention (CDC) have identified B. pseudomallei as a select biological agent, with a high potential for misuse against masses. Melioidosis is associated with a severe clinical syndrome which is dependant in part on the route of exposure, dose, and immune status of the host, although much remains unclear about pathogenesis of the disease. Although infection from subcutaneous inoculation is not uncommon, inhalation produces the most severe disease. Presently, in vivo study of melioidosis has been mostly restricted to rodent disease models (e.g., hamster, guinea pig). Deciphering the pathogenesis of melioidosis continues to evolve; the role of TLRs in mediating infection and facilitating intracellular entry is of particular importance. We exposed three strains of mice (BALB/c, C57BL/6 or TLR-4 KO transgenics (C3H-Hej)) to aerosolized B. thailandensis to further define the role of Th1-associated host response. Results indicate an increased susceptibility in the C57BL/6 animals, with increased local cytokine response and lethality at lower doses than the TLR-4 KO or BALB/c animals. Dose dependant lung pathology indicated an acute infection in the lungs of the C57BL/6 group compared to signs of chronic infection in the BALB/C mice. TLR-4 KO animals were unaffected by the aerosolized B. thailandensis at the highest doses (1.0E+09 CFU). These results suggest that TLR-4 may not play a prominent role in Burkholderia-related infection, that B. thailandensis can be used as a surrogate agent for experimental laboratory investigation of melioidosis in small animal models, and provides critical information twoard the goal of developing a nonhuman primate model of B. pseudomallei infection.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目和研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。类鼻疽是一种因接触类鼻疽伯克霍尔德氏菌而引起的传染病，这是一种主要发现于东南亚和澳大利亚北部的腐生菌。类鼻疽被认为是一种新出现的传染病和人畜共患病病原体。过去十年来，类鼻疽杆菌相关的细菌性败血症和支气管肺炎的发病率在流行地区显着增加。类鼻疽伯克氏菌是一种生物威胁因子，主要是因为其在低剂量（少于 100 个细菌细胞）下具有显着的传染性。因此，美国疾病控制与预防中心 (CDC) 已将类鼻疽伯克氏菌确定为一种精选的生物制剂，很可能被滥用于人群。类鼻疽与严重的临床综合征相关，该综合征部分取决于暴露途径、剂量和宿主的免疫状态，尽管该疾病的发病机制仍不清楚。尽管皮下接种引起的感染并不少见，但吸入会导致最严重的疾病。目前，类鼻疽的体内研究主要局限于啮齿动物疾病模型（例如仓鼠、豚鼠）。类鼻疽发病机制的解析仍在不断发展； TLR 在介导感染和促进细胞内进入方面的作用尤为重要。我们将三种小鼠品系（BALB/c、C57BL/6 或 TLR-4 KO 转基因小鼠 (C3H-Hej)）暴露于雾化的泰国芽孢杆菌中，以进一步确定 Th1 相关宿主反应的作用。结果表明，与 TLR-4 KO 或 BALB/c 动物相比，C57BL/6 动物的易感性增加，局部细胞因子反应和致死率在较低剂量下增加。剂量依赖性肺部病理学表明，与 BALB/C 小鼠的慢性感染迹象相比，C57BL/6 组的肺部存在急性感染。 TLR-4 KO 动物未受到最高剂量 (1.0E+09 CFU) 雾化的泰国伯氏杆菌的影响。这些结果表明，TLR-4 在伯克霍尔德杆菌相关感染中可能不会发挥显着作用，泰国伯克霍尔德杆菌可用作小动物模型类鼻疽实验实验室研究的替代剂，并为开发目标提供关键信息。类鼻疽杆菌感染的非人类灵长类动物模型。