Sullivan Joseph Pierce, Nair Nisha, Potula Hari-Hara, Gomes-Solecki Maria
Department of Comparative Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee, USA.
Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Infect Immun. 2017 Mar 23;85(4). doi: 10.1128/IAI.01050-16. Print 2017 Apr.
Leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H/HeJ mice with serovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and dissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. The infectious dose that led to consistent dissemination to kidney after conjunctival infection was ∼10 leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified ∼10 and ∼10 leptospires per μl of urine and per μg of kidney, respectively. Leptospira-specific IgM and IgG were detected at 15 days postinfection, and isotyping of the Ig subclass showed that the total IgG response switched from an IgG1 response to an IgG3 response after infection with Histological periodic acid-Schiff D staining of infected kidney showed interstitial nephritis, mononuclear cell infiltrates, and reduced size of glomeruli. Quantification of proinflammatory immunomediators in kidney showed that keratinocyte-derived chemokine, macrophage inflammatory protein 2, RANTES, tumor necrosis factor alpha, gamma interferon, and interleukin-10 were upregulated in infected mice. We show that the kinetics of disease progression after infection via the ocular conjunctiva is delayed compared with infection via the standard intraperitoneal route. Differences may be related to the number of spirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.
钩端螺旋体病是一种潜在的致命性人畜共患病，可通过皮肤和黏膜表面接触被感染尿液污染的土壤和水而获得。我们使用地方性传播模式（结膜途径）分析了C3H/HeJ小鼠感染哥本哈根血清型钩端螺旋体的结果。感染导致体重减轻以及从血液传播至尿液，并且在血液和尿液中同时检测到螺旋体。结膜感染后导致一致传播至肾脏的感染剂量约为10个钩端螺旋体。有趣的是，鉴于我们分别在每微升尿液和每微克肾脏中定量出约10个和约10个钩端螺旋体，似乎定殖于肾脏的螺旋体数量较少。感染后15天检测到钩端螺旋体特异性IgM和IgG，并且Ig亚类的同型分析表明，感染后总IgG反应从IgG1反应转变为IgG3反应。感染肾脏的组织学高碘酸 - 希夫D染色显示间质性肾炎、单核细胞浸润以及肾小球体积减小。肾脏中促炎免疫介质的定量分析表明，角质形成细胞衍生趋化因子、巨噬细胞炎性蛋白2、调节激活正常T细胞表达和分泌的因子、肿瘤坏死因子α、γ干扰素和白细胞介素 - 10在感染小鼠中上调。我们表明，与通过标准腹腔途径感染相比，经眼结膜感染后疾病进展的动力学延迟。差异可能与成功克服眼结膜天然防御并穿过组织的螺旋体数量有关。
