Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA.
Am J Pathol. 2010 Jun;176(6):2753-63. doi: 10.2353/ajpath.2010.090862. Epub 2010 Apr 15.
Bartonella are ubiquitous gram-negative pathogens that cause chronic blood stream infections in mammals. Two species most often responsible for human infection, B. henselae and B. quintana, cause prolonged febrile illness in immunocompetent hosts, known as cat scratch disease and trench fever, respectively. Fascinatingly, in immunocompromised hosts, these organisms also induce new blood vessel formation leading to the formation of angioproliferative tumors, a disease process named bacillary angiomatosis. In addition, they cause an endothelial-lined cystic disease in the liver known as bacillary peliosis. Unfortunately, there are as yet no completely satisfying small animal models for exploring these unique human pathologies, as neither species appears able to sustain infection in small animal models. Therefore, we investigated the potential use of other Bartonella species for their ability to recapitulate human pathologies in an immunodeficient murine host. Here, we demonstrate the ability of Bartonella taylorii to cause chronic infection in SCID/BEIGE mice. In this model, Bartonella grows in extracellular aggregates, embedded within collagen matrix, similar to previous observations in cat scratch disease, bacillary peliosis, and bacillary angiomatosis. Interestingly, despite overwhelming infection later in disease, evidence for significant intracellular replication in endothelial or other cell types was not evident. We believe that this new model will provide an important new tool for investigation of Bartonella-host interaction.
巴尔通体是一种普遍存在的革兰氏阴性病原体,可引起哺乳动物慢性血流感染。两种最常导致人类感染的物种,即汉赛巴尔通体和五日热巴通体,分别在免疫功能正常的宿主中引起长期发热疾病,分别称为猫抓病和战壕热。有趣的是,在免疫功能低下的宿主中,这些生物体还诱导新血管形成,导致血管增生性肿瘤的形成,这一疾病过程被命名为杆菌性血管瘤病。此外,它们还导致肝脏内皮衬里的囊性疾病,称为杆菌性肝血窦扩张症。不幸的是,目前还没有完全令人满意的小动物模型来探索这些独特的人类病理,因为这两种物种似乎都不能在小动物模型中维持感染。因此,我们研究了其他巴尔通体物种的潜在用途,以了解它们在免疫缺陷小鼠宿主中重现人类病理的能力。在这里,我们证明了泰勒巴尔通体在 SCID/BEIGE 小鼠中引起慢性感染的能力。在这种模型中,巴尔通体在细胞外聚集体中生长,嵌入在胶原基质中,类似于猫抓病、杆菌性肝血窦扩张症和杆菌性血管瘤病的先前观察结果。有趣的是,尽管在疾病后期感染严重,但在内皮或其他细胞类型中没有明显的细胞内复制证据。我们相信,这种新模型将为研究巴尔通体与宿主的相互作用提供一个重要的新工具。