Ozuru Ryo, Saito Mitsumasa, Kanemaru Takaaki, Miyahara Satoshi, Villanueva Sharon Y A M, Murray Gerald L, Adler Ben, Fujii Jun, Yoshida Shin-Ichi
Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, Tottori, Japan.
PLoS One. 2017 Feb 28;12(2):e0172973. doi: 10.1371/journal.pone.0172973. eCollection 2017.
Leptospirosis is one of the most widespread zoonoses in the world, and its most severe form in humans, "Weil's disease," may lead to jaundice, hemorrhage, renal failure, pulmonary hemorrhage syndrome, and sometimes,fatal multiple organ failure. Although the mechanisms underlying jaundice in leptospirosis have been gradually unraveled, the pathophysiology and distribution of leptospires during the early stage of infection are not well understood. Therefore, we investigated the hamster leptospirosis model, which is the accepted animal model of human Weil's disease, by using an in vivo imaging system to observe the whole bodies of animals infected with Leptospira interrogans and to identify the colonization and growth sites of the leptospires during the early phase of infection. Hamsters, infected subcutaneously with 104 bioluminescent leptospires, were analyzed by in vivo imaging, organ culture, and microscopy. The results showed that the luminescence from the leptospires spread through each hamster's body sequentially. The luminescence was first detected at the injection site only, and finally spread to the central abdomen, in the liver area. Additionally, the luminescence observed in the adipose tissue was the earliest detectable compared with the other organs, indicating that the leptospires colonized the adipose tissue at the early stage of leptospirosis. Adipose tissue cultures of the leptospires became positive earlier than the blood cultures. Microscopic analysis revealed that the leptospires colonized the inner walls of the blood vessels in the adipose tissue. In conclusion, this is the first study to report that adipose tissue is an important colonization site for leptospires, as demonstrated by microscopy and culture analyses of adipose tissue in the hamster model of Weil's disease.
钩端螺旋体病是世界上分布最广泛的人畜共患病之一,其在人类中最严重的形式“韦尔病”可能导致黄疸、出血、肾衰竭、肺出血综合征,有时还会导致致命的多器官功能衰竭。尽管钩端螺旋体病黄疸的潜在机制已逐渐被揭示,但感染早期钩端螺旋体的病理生理学和分布情况仍不清楚。因此,我们通过使用体内成像系统观察感染问号钩端螺旋体的动物全身,并确定感染早期钩端螺旋体的定植和生长部位,对仓鼠钩端螺旋体病模型(这是公认的人类韦尔病动物模型)进行了研究。皮下注射104个生物发光钩端螺旋体的仓鼠通过体内成像、器官培养和显微镜检查进行分析。结果表明,钩端螺旋体发出的光依次在每只仓鼠体内传播。发光最初仅在注射部位检测到,最终扩散到腹部中央肝脏区域。此外,与其他器官相比,在脂肪组织中观察到的发光是最早可检测到的,这表明钩端螺旋体在钩端螺旋体病早期定植于脂肪组织。钩端螺旋体的脂肪组织培养比血培养更早呈阳性。显微镜分析显示,钩端螺旋体定植于脂肪组织中血管的内壁。总之,这是第一项通过对韦尔病仓鼠模型的脂肪组织进行显微镜和培养分析,报告脂肪组织是钩端螺旋体重要定植部位的研究。