Barnes Jodie L, Williams Natasha L, Ketheesan Natkunam
School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Qld, Australia.
FEMS Immunol Med Microbiol. 2008 Apr;52(3):379-88. doi: 10.1111/j.1574-695X.2008.00389.x. Epub 2008 Feb 22.
Melioidosis is caused by the facultative intracellular bacterium, Burkholderia pseudomallei. Using C57BL/6 mice, we investigated the role of macrophages, TNF-alpha, TNF receptor-1 (TNFR1) and TNF receptor-2 (TNFR2) in host defense against B. pseudomallei using an experimental model of melioidosis. This study has demonstrated that in vivo depletion of macrophages renders C57BL/6 mice highly susceptible to intranasal infection with B. pseudomallei, with significant mortality occurring within 5 days of infection. Using knockout mice, we have also shown that TNF-alpha and both TNFR1 and TNFR2 are required for optimal control of B. pseudomallei infection. Compared with control mice, increased bacterial loads were demonstrated in spleen and liver of knockout mice at day 2 postinfection, correlating with increased inflammatory infiltrates comprised predominantly of neutrophils and widespread necrosis. Following infection with B. pseudomallei, mortality rates of 85.7%, 70% and 91.7% were observed for mice deficient in TNF-alpha, TNFR1 and TNFR2, respectively. Comparison of survival, bacterial loads and histology indicate that macrophages, TNF-alpha, TNFR1 or TNFR2 play a role in controlling rapid dissemination of B. pseudomallei.
类鼻疽是由兼性细胞内细菌伯克霍尔德菌引起的。我们使用C57BL/6小鼠，通过类鼻疽实验模型研究了巨噬细胞、肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子受体-1（TNFR1）和肿瘤坏死因子受体-2（TNFR2）在宿主抵御伯克霍尔德菌中的作用。本研究表明，体内巨噬细胞耗竭使C57BL/6小鼠对经鼻感染伯克霍尔德菌高度易感，感染后5天内出现显著死亡率。使用基因敲除小鼠，我们还表明TNF-α以及TNFR1和TNFR2都是最佳控制伯克霍尔德菌感染所必需的。与对照小鼠相比，感染后第2天基因敲除小鼠的脾脏和肝脏中细菌载量增加，这与主要由中性粒细胞组成的炎症浸润增加和广泛坏死相关。感染伯克霍尔德菌后，TNF-α、TNFR1和TNFR2缺陷小鼠的死亡率分别为85.7%、70%和91.7%。生存、细菌载量和组织学的比较表明，巨噬细胞、TNF-α、TNFR1或TNFR2在控制伯克霍尔德菌的快速传播中发挥作用。
