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Mouse Model of Coxiella burnetii Aerosolization

机译:伯氏柯氏杆菌气雾化的小鼠模型

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Coxiella burnetii is mainly transmitted by aerosols and is responsible for multiple-organ lesions. Animal models have shown C. burnetii pathogenicity, but long-term outcomes still need to be clarified. We used a whole-body aerosol inhalation exposure system to mimic the natural route of infection in immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice. After an initial lung inoculum of 104 C. burnetii cells/lung, the outcome, serological response, hematological disorders, and deep organ lesions were described up to 3 months postinfection. C. burnetii-specific PCR, anti-C. burnetii immunohistochemistry, and fluorescent in situ hybridization (FISH) targeting C. burnetii-specific 16S rRNA completed the detection of the bacterium in the tissues. In BALB/c mice, a thrombocytopenia and lymphopenia were first observed, prior to evidence of C. burnetii replication. In all SCID mouse organs, DNA copies increased to higher levels over time than in BALB/c ones. Clinical signs of discomfort appeared in SCID mice, so follow-up had to be shortened to 2 months in this group. At this stage, all animals presented bone, cervical, and heart lesions. The presence of C. burnetii could be attested in situ for all organs sampled using immunohistochemistry and FISH. This mouse model described C. burnetii Nine Mile strain spread using aerosolization in a way that corroborates the pathogenicity of Q fever described in humans and completes previously published data in mouse models. C. burnetii infection occurring after aerosolization in mice thus seems to be a useful tool to compare the pathogenicity of different strains of C. burnetii.
机译:伯氏柯氏杆菌主要通过气溶胶传播,并引起多器官损伤。动物模型已经显示出伯氏梭菌的致病性,但长期结果仍需阐明。我们使用了全身气雾吸入暴露系统来模拟免疫力(BALB / c)和严重的联合免疫缺陷(SCID)小鼠的自然感染途径。最初接种10 4 伯氏梭菌细胞/肺后,在感染后3个月内描述了结局,血清学反应,血液学异常和深部器官病变。 C. Burnetii特异性PCR,抗C。 Burnetii免疫组织化学和靶向C. Burnetii特异性16S rRNA的荧光原位杂交(FISH)完成了组织中细菌的检测。在BALB / c小鼠中,首先观察到血小板减少和淋巴细胞减少,然后才显示出伯氏梭菌复制。随着时间的推移,在所有SCID小鼠器官中,DNA拷贝的水平均高于BALB / c小鼠。 SCID小鼠出现不适的临床体征,因此该组的随访时间必须缩短至2个月。在此阶段,所有动物均出现骨,颈和心脏病变。可以使用免疫组织化学和FISH对所有采样的器官进行原位证明。该小鼠模型描述了使用雾化方法传播的伯氏梭菌九英里菌株,从而证实了人类所描述的Q热的致病性,并完成了先前在小鼠模型中发表的数据。因此,在小鼠中气雾化后发生的伯氏梭菌感染似乎是比较不同菌株伯氏梭菌致病性的有用工具。

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