Zeidner Nordin S, Núncio Maria S, Schneider Bradley S, Gern Lise, Piesman Joseph, Brandão Otilia, Filipe Armindo R
Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, CO 80522, USA, *Instituto Nacional de Saúde, Dr. Ricardo Jorge, Centro de Estudos de Vectores e Doencas Infecciosas, Águas de Moura, Portugal, †Institut de Zoologie, University of Neuchâtel, Neuchâtel, Switzerland and ‡Department of Pathology, São Bernardo Hospital, Setúbal, Portugal.
J Med Microbiol. 2001 Dec;50(12):1055-1060. doi: 10.1099/0022-1317-50-12-1055.
A low-passage, Portuguese isolate of Borrelia lusitaniae, strain PotiB2, was inoculated into C3H/HeN mice and disease was monitored by histopathology at 8 weeks after spirochaete challenge. Ear, heart, bladder, femoro-tibial joint, brain and spinal cord were examined. B. lusitaniae strain PotiB2 (6 of 10 mice) and B. burgdorferi sensu stricto strain N40 (9 of 10 mice) induced similar lesions in the bladder of infected mice characterised as a multifocal, lymphoid, interstitial cystitis. Moreover, both B. lusitaniae PotiB2 and B. burdorferi N40 induced lesions in the heart of infected mice. The lesions induced by B. lusitaniae PotiB2 (2 of 10 mice) were characterised as a severe, necrotising endarteritis of the aorta, with a minimal, mixed inflammatory infiltrate (neutrophils, macrophages and lymphoid cells) extending into the adjacent myocardium. In contrast, B. burgdorferi N40 induced a periarteritis of the pulmonary artery (7 of 10 mice), with no involvement of the endothelium and more extensive inflammation and subsequent necrosis of the adjacent myocardium. This infiltrate was composed entirely of mononuclear cells, predominantly mature lymphocytes and plasma cells. No lesions were noted in the joints or central nervous system with inoculation of strains N40 or PotiB2, and co-inoculation of either strain with Ixodes ricinus salivary gland lysate did not affect the resulting pathology. Serology, examined 8 weeks after inoculation, indicated a different reactivity in mice infected with B. lusitaniae PotiB2 compared with B. burgdorferi N40. Immunoblot analysis demonstrated that mice with lesions resulting from infection with B. lusitaniae PotiB2 reacted only to the flagellin protein (41 kDa) or to flagellin and OspC, whereas mice infected with B. burgdorferi N40 reacted with multiple high and low mol. wt proteins, including flagellin, p93, p39, OspA, OspB and OspC. These results indicate that B. lusitaniae PotiB2 induced pathology similar to B. burgdorferi N40 when inoculated into susceptible mice. Moreover, these results establish the first animal model of disease with B. lusitaniae. This mouse model can be used to characterise the immunopathogenesis of B. lusitaniae infection and to delineate the proteins responsible for disease induction in susceptible mice.
将一株低传代的葡萄牙疏螺旋体菌株伯氏疏螺旋体（Borrelia lusitaniae）PotiB2接种到C3H/HeN小鼠体内，并在螺旋体攻击8周后通过组织病理学监测疾病情况。对耳朵、心脏、膀胱、股骨 - 胫骨关节、大脑和脊髓进行了检查。伯氏疏螺旋体PotiB2菌株（10只小鼠中有6只）和狭义伯氏疏螺旋体Nielsen菌株（10只小鼠中有9只）在感染小鼠的膀胱中诱导出相似的病变，其特征为多灶性、淋巴性、间质性膀胱炎。此外，伯氏疏螺旋体PotiB2和狭义伯氏疏螺旋体Nielsen均在感染小鼠的心脏中诱导出病变。伯氏疏螺旋体PotiB2诱导的病变（10只小鼠中有2只）表现为主动脉严重的坏死性动脉内膜炎，伴有少量混合性炎性浸润（中性粒细胞、巨噬细胞和淋巴细胞）延伸至相邻心肌。相比之下，狭义伯氏疏螺旋体Nielsen诱导肺动脉周围炎（10只小鼠中有7只）；不累及内皮，相邻心肌有更广泛的炎症及随后的坏死。这种浸润完全由单核细胞组成，主要是成熟淋巴细胞和浆细胞。接种Nielsen或PotiB2菌株后，在关节或中枢神经系统未发现病变，并且将任一菌株与蓖麻硬蜱唾液腺裂解物共同接种并不影响所产生的病理变化。接种8周后进行的血清学检测表明，感染伯氏疏螺旋体PotiB2的小鼠与感染狭义伯氏疏螺旋体Nielsen的小鼠反应不同。免疫印迹分析表明，因感染伯氏疏螺旋体PotiB2而出现病变的小鼠仅对鞭毛蛋白（41 kDa）或鞭毛蛋白和OspC产生反应，而感染狭义伯氏疏螺旋体Nielsen的小鼠则与多种高分子量和低分子量蛋白质发生反应，包括鞭毛蛋白、p93、p39、OspA、OspB和OspC。这些结果表明，将伯氏疏螺旋体PotiB2接种到易感小鼠体内时，其诱导的病理变化与狭义伯氏疏螺旋体Nielsen相似。此外，这些结果建立了首个伯氏疏螺旋体疾病动物模型。该小鼠模型可用于表征伯氏疏螺旋体感染的免疫发病机制，并确定在易感小鼠中引发疾病的蛋白质。
