Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice
Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice
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DOI：
10.1128/iai.01050-16
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发表时间：
2017-04-01
影响因子：
3.1
通讯作者：
Gomes-Solecki, Maria
中科院分区：
文献类型：
--
作者：
Sullivan, Joseph Pierce;Nair, Nisha;Gomes-Solecki, Maria
钩端螺旋体病是一种潜在的致命性人畜共患病，通过皮肤和粘膜表面与受感染尿液污染的土壤和水接触而获得。我们使用一种地方性传播途径--结膜途径，分析了C3H/HeJ小鼠感染问号钩端螺旋体不同血清型的结局。感染导致体重减轻，问号钩端螺旋体从血液传播到尿液，同时在血液和尿液中检测到螺旋体。导致结膜感染后持续扩散到肾脏的感染剂量类似于10(8)个钩端螺旋体。有趣的是，由于我们分别量化了L每亩尿10个钩端螺旋体和每亩肾脏10个钩端螺旋体，似乎有较少数量的螺旋体定植在肾脏。在感染钩端螺旋体后15天检测到钩端螺旋体特异性IgM和免疫球蛋白G，免疫球蛋白亚类的同型分析表明，钩端螺旋体感染问号钩端螺旋体后，总的免疫球蛋白G应答由IgG1应答转变为IgG3应答。感染肾组织学检查示间质性肾炎，单核细胞浸润，肾小球体积缩小。肾组织中促炎症免疫介质的定量检测显示，角质形成细胞源性趋化因子、巨噬细胞炎症蛋白2、RANTES、肿瘤坏死因子α、γ干扰素和白细胞介素10在感染小鼠中表达上调。我们发现，与通过标准的腹膜内途径感染相比，通过眼结膜感染后的疾病进展动力学是延迟的。差异可能与问号钩端螺旋体的数量有关，这些螺旋体成功地克服了眼结膜的自然防御并通过组织传播。
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 Leptospira interrogans serovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and L. interrogans 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 similar to 10(8) leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified similar to 10(5) and similar to 10 leptospires per mu l of urine and per mu g 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 L. interrogans. 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 L. interrogans spirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.