Chiang Chih-Yuan, Ulrich Ricky L, Ulrich Melanie P, Eaton Brett, Ojeda Jenifer F, Lane Douglas J, Kota Krishna P, Kenny Tara A, Ladner Jason T, Dickson Samuel P, Kuehl Kathleen, Raychaudhuri Rahul, Sun Mei, Bavari Sina, Wolcott Mark J, Covell David, Panchal Rekha G
Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA.
Institute for Therapeutic Innovation, Department of Medicine, University of Florida, Orlando, FL, USA.
BMC Microbiol. 2015 Nov 6;15:259. doi: 10.1186/s12866-015-0593-3.
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered.
The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt.
These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.
类鼻疽伯克霍尔德菌（Bp）和鼻疽伯克霍尔德菌（Bm）是革兰氏阴性兼性胞内病原体，分别是类鼻疽和鼻疽的病原体。根据暴露途径，即气溶胶或经皮暴露，Bp或Bm感染可导致广泛的疾病——从急性到慢性，从复发性疾病到致命性败血症。这两种疾病都与诊断困难和高死亡率相关。约95%的患者死于未经治疗的败血症感染，即使给予标准抗生素治疗，死亡率仍为50%。
本研究的目的是描述小鼠巨噬细胞介导的表型和分子反应，这些反应是从人类、动物、环境和不同地理位置获得的一系列Bp、Bm、泰国伯克霍尔德菌（Bt）和俄克拉荷马伯克霍尔德菌（Bo）菌株的特征。伯克霍尔德菌属（N = 21）能够在巨噬细胞中侵袭和复制，尽管程度不同。所有Bp（N = 9）和4株Bm菌株在感染后能够诱导细菌表面的肌动蛋白聚合。几株Bp和Bm菌株诱导多核巨细胞（MNGC）形成的能力降低，而Bo和Bp 776菌株无法诱导这种表型。宿主细胞因子反应的测量显示，与Bp菌株相比，Bm介导的IL-6和IL-10产生具有统计学意义。对84种小鼠细胞因子、趋化因子及其相应受体的转录数据进行层次聚类，确定了29个宿主基因作为伯克霍尔德菌属之间差异反应的指标。进一步验证证实，与Bp和Bt相比，Bm介导的Il-1b、Il-10、Tnfrsf1b和Il-36a mRNA表达显著更高。
这些结果描述了宿主对致病性和无毒伯克霍尔德菌菌株先天反应中的表型和免疫差异，并深入了解了宿主-伯克霍尔德菌相互作用背后的表型改变和分子靶点。
