Rocha F Janaina Soares, Schleicher Ulrike, Mattner Jochen, Alber Gottfried, Bogdan Christian
Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Wasserturmstrasse 3-5, D-91054 Erlangen, Germany.
Infect Immun. 2007 Aug;75(8):3823-32. doi: 10.1128/IAI.01335-06. Epub 2007 May 21.
Cutaneous leishmaniasis is caused by protozoan parasites of the genus Leishmania. The mechanisms of pathogen control have been established primarily in the mouse model of Leishmania major infection, but they might not hold true for other Leishmania species associated with cutaneous disease. Here, we analyzed the role of cytokines, signaling components, and effector molecules in the control of New World cutaneous leishmaniasis due to L. braziliensis. Unlike L. major, L. braziliensis caused small, nonulcerative, and self-healing skin swelling in C57BL/6 mice, as well as BALB/c mice. In contrast to the results obtained for L. mexicana, mice deficient for interleukin-12 or its key signaling molecule, signal transducer and activator of transcription 4, rapidly succumbed to severe visceral leishmaniasis. Infection of tumor necrosis factor knockout mice with L. braziliensis led to progressive, nonhealing skin lesions with erosions and hemorrhagic ulcerations, but in contrast to the results with L. major, only 20 to 30% of the mice developed fatal visceral disease. As seen with L. major, mice with a deleted inducible nitric oxide synthase gene (iNOS(-/-)) were unable to contain L. braziliensis in the skin, whereas the control of the parasite in the spleen remained unimpaired. Unlike what happens in L. major infections, NADPH oxidase had no impact on the course of disease in L. braziliensis-infected mice. These results not only define essential components of a protective immune response to L. braziliensis but also illustrate that the requirements for the control of cutaneous leishmaniasis vary between different parasite species.
皮肤利什曼病由利什曼原虫属的原生动物寄生虫引起。病原体控制机制主要是在硕大利什曼原虫感染的小鼠模型中建立的，但对于与皮肤疾病相关的其他利什曼原虫物种可能并不适用。在这里，我们分析了细胞因子、信号传导成分和效应分子在控制巴西利什曼原虫引起的新大陆皮肤利什曼病中的作用。与硕大利什曼原虫不同，巴西利什曼原虫在C57BL/6小鼠以及BALB/c小鼠中引起小的、非溃疡性的、可自愈的皮肤肿胀。与墨西哥利什曼原虫的结果相反，白细胞介素-12或其关键信号分子——信号转导和转录激活因子4缺陷的小鼠迅速死于严重的内脏利什曼病。用巴西利什曼原虫感染肿瘤坏死因子基因敲除小鼠会导致进行性的、不愈合的皮肤病变，伴有糜烂和出血性溃疡，但与硕大利什曼原虫的结果不同，只有20%至30%的小鼠发展为致命的内脏疾病。正如在硕大利什曼原虫感染中所见，诱导型一氧化氮合酶基因缺失的小鼠（iNOS(-/-)）无法在皮肤中控制巴西利什曼原虫，而脾脏中对寄生虫的控制仍然未受损害。与硕大利什曼原虫感染不同的是氧化型辅酶Ⅱ烟酰胺腺嘌呤二核苷酸磷酸氧化酶对巴西利什曼原虫感染小鼠的病程没有影响。这些结果不仅确定了对巴西利什曼原虫保护性免疫反应的重要组成部分，也说明了控制皮肤利什曼病的要求在不同的寄生虫物种之间有所不同。
