Department of Microbiology and Immunology, Tulane University School of Medicine, Covington, LA 70112, USA.
Microb Pathog. 2010 Jan;48(1):9-17. doi: 10.1016/j.micpath.2009.10.004. Epub 2009 Oct 21.
Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial disease that accounts for high rates of septicaemia and death in parts of Southeast Asia and Northern Australia. The closely related species Burkholderia thailandensis is considered avirulent in humans and has been used as a surrogate for B. pseudomallei in several studies. The pathogenesis of B. pseudomallei and the role of Toll-like receptors (TLRs) in host immunity to infection are not well-defined. In this study, we exposed four strains of inbred mice (BALB/c, C57BL/6, TLR4-deficient C3H/HeJ, and TLR4-competent C3H/HeN) to increasing doses of aerosolized B. thailandensis to determine strain susceptibility and the role of TLR4 during pulmonary infection. Our results indicate an increased susceptibility in the C57BL/6 and BALB/c strains, who displayed lethality, bacterial burden in organs, and pulmonary and systemic inflammation. C3H/HeJ were as resistant as C3H/HeN mice to B. thailandensis at the highest challenge dose examined, but TLR4-deficient animals exhibited a modest increase in chronic pulmonary inflammation. These results demonstrate that B. thailandensis can be used as a surrogate for experimental laboratory investigation of melioidosis in small animal models and that TLR4 may not play a prominent role during acute pneumonic melioidosis.
类鼻疽伯克霍尔德菌是类鼻疽病的病原体，这是一种新兴的细菌性疾病，在东南亚和澳大利亚北部的部分地区，类鼻疽病的败血症和死亡率很高。密切相关的物种——泰国伯克霍尔德菌被认为对人类无毒性，并已在几项研究中被用作类鼻疽伯克霍尔德菌的替代品。类鼻疽伯克霍尔德菌的发病机制和 Toll 样受体 (TLR) 在宿主抗感染免疫中的作用尚未明确。在这项研究中，我们使 4 种近交系小鼠（BALB/c、C57BL/6、TLR4 缺陷型 C3H/HeJ 和 TLR4 功能正常型 C3H/HeN）暴露于递增剂量的雾化泰国伯克霍尔德菌气溶胶中，以确定菌株易感性和 TLR4 在肺部感染中的作用。我们的研究结果表明，C57BL/6 和 BALB/c 品系的易感性增加，这两个品系表现出致死率、器官细菌负荷以及肺部和全身炎症。在研究的最高挑战剂量下，C3H/HeJ 与 C3H/HeN 小鼠一样对泰国伯克霍尔德菌具有抗性，但 TLR4 缺陷型动物的慢性肺部炎症略有增加。这些结果表明，泰国伯克霍尔德菌可作为实验性实验室研究小动物模型中类鼻疽病的替代物，并且 TLR4 在急性肺炎性类鼻疽病中可能不起主要作用。
