MELIODOSIS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 类鼻疽是一种由暴露于类鼻疽伯克霍尔德氏菌引起的传染病，类鼻疽伯克霍尔德氏菌是一种主要在东南亚和北方澳大利亚发现的寄生虫。 类鼻疽被认为是一种新兴的传染病和动物流行病。B的发生率。在过去十年中，假鼻疽相关的细菌性脓毒症和支气管肺炎在流行地区显著增加。B。鼻疽假单胞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）下具有显著的感染性。因此，疾病控制和预防中心（CDC）已经确定了B。作为一种选定的生物制剂，具有对群众滥用的高可能性。 类鼻疽病是一种严重的临床综合征，部分依赖于暴露途径、剂量和宿主的免疫状态，尽管该疾病的发病机制仍不清楚。 虽然皮下接种引起的感染并不少见，但吸入引起的疾病最严重。目前，类鼻疽的体内研究主要限于啮齿动物疾病模型（例如，仓鼠、豚鼠）。阐明类鼻疽的发病机制仍在继续发展; TLR在介导感染和促进细胞内进入中的作用特别重要。 我们将三种品系的小鼠（BALB/c、C57 BL/6或TLR-4 KO转基因（C3 H-Hej））暴露于雾化的B。thailandensis进一步定义了Th 1相关宿主应答的作用。 结果表明，C57 BL/6动物的易感性增加，局部细胞因子反应和致死率在低于TLR-4 KO或BALB/c动物的剂量下增加。 剂量依赖性肺病理学表明，与BALB/C小鼠中的慢性感染体征相比，C57 BL/6组的肺中存在急性感染。 TLR-4 KO动物不受雾化B的影响。在最高剂量（1.0E+09 CFU）下， 这些结果提示TLR-4在伯克霍尔德氏菌相关感染中可能不起显著作用，而B. thailandensis可用作小动物模型中类鼻疽实验室研究的替代剂，并为开发B的非人灵长类动物模型的目标提供关键信息。类鼻疽感染。

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.