Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis.
Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis.
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DOI：
10.1084/jem.188.10.1941
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发表时间：
1998-11-16
期刊：
影响因子：
--
通讯作者：
Sacks DL
中科院分区：
文献类型：
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作者：
Belkaid Y;Kamhawi S;Modi G;Valenzuela J;Noben-Trauth N;Rowton E;Ribeiro J;Sacks DL
我们已经开发了一个模型，皮肤利什曼病由于利什曼原虫主要，试图模仿自然条件下的感染。将1，000个后生环前鞭毛体与从天然载体Papatasii获得的唾液腺超声处理物（SGS）共同接种到未处理小鼠或预先暴露于SGS的小鼠的耳真皮中。这些研究揭示了SGS对皮肤部位病变发展的显著加剧作用，并且在预先暴露于唾液组分的小鼠中完全消除了这种作用。在BALB/c和C57 Bl/6（B/6）小鼠中，在SGS存在下感染后，皮肤病变出现更早，更具破坏性，并且含有更多数量的寄生虫。此外，SGS的共接种将B/6小鼠转化为不愈合表型。在IL-4缺陷或SCID小鼠中均未观察到SGS的作用。在BALB/c和B/6小鼠中的疾病恶化与表皮细胞产生2型细胞因子的频率的早期（6小时）增加相关。SGS在先前注射SGS的小鼠表皮中没有引起2型细胞因子。这些小鼠产生的抗唾液抗体能够中和SGS增强感染的能力，并在表皮中引发IL-4和IL-5反应。这些结果首次表明，对于有病媒传播感染风险的个体，接触病媒唾液的历史可能会影响接触传播寄生虫的结果。
We have developed a model of cutaneous leishmaniasis due to Leishmania major that seeks to mimic the natural conditions of infection. 1,000 metacyclic promastigotes were coinoculated with a salivary gland sonicate (SGS) obtained from a natural vector, Phlebotomus papatasii, into the ear dermis of naive mice or of mice preexposed to SGS. The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice preexposed to salivary components. In both BALB/c and C57Bl/6 (B/6) mice, the dermal lesions appeared earlier, were more destructive, and contained greater numbers of parasites after infection in the presence of SGS. Furthermore, coinoculation of SGS converted B/6 mice into a nonhealing phenotype. No effect of SGS was seen in either IL-4– deficient or in SCID mice. Disease exacerbation in both BALB/c and B/6 mice was associated with an early (6 h) increase in the frequency of epidermal cells producing type 2 cytokines. SGS did not elicit type 2 cytokines in the epidermis of mice previously injected with SGS. These mice made antisaliva antibodies that were able to neutralize the ability of SGS to enhance infection and to elicit IL-4 and IL-5 responses in the epidermis. These results are the first to suggest that for individuals at risk of vector-borne infections, history of exposure to vector saliva might influence the outcome of exposure to transmitted parasites.