Murine model of chronic L. (Viannia) panamensis infection: role of IL-13 in disease.

Murine model of chronic L. (Viannia) panamensis infection: role of IL-13 in disease.
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DOI:
10.1002/eji.201040384
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发表时间:
2010-10
影响因子:
5.4
通讯作者:
McMahon-Pratt, Diane
McMahon-Pratt, Diane
中科院分区:
医学3区
文献类型:
--
作者:
Castilho, Tiago M.;Goldsmith-Pestana, Karen;Lozano, Caterin;Valderrama, Liliana;Saravia, Nancy G.;McMahon-Pratt, Diane

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利什曼原虫(Viannia)生物体是美洲人类皮肤利什曼病最常见的病原体。然而,我们对 L. (Viannia) 生物体利用的免疫机制的了解仍然有限,并且疾病背后的机制尚不清楚。在此,我们报告了巴拿马乳杆菌感染的 BALB/c 小鼠模型的开发,该模型能够复制慢性疾病,具有持续感染和临床明显病变超过 1 年的能力。小鼠的免疫反应与患有慢性和复发性病变的 L. (V.) panamensis 感染患者的免疫反应类似,呈现混合的 Th1/Th2 反应,并存在 TNF-α、IFN-γ、IL-10 和 IL-13。使用免疫缺陷小鼠,IL-13 和/或 IL-4Rα 在确定慢性感染易感性方面的关键作用是显而易见的。随着免疫缺陷小鼠的愈合诱导,发现 IFN-γ 和 IL-17 增加,同时寄生虫得到控制和消除。具体而言,观察到产生 IFN-γ 的 CD4+(而非 CD8+)T 细胞增加。这些结果表明 IL-13 是控制巴拿马 L. (V.) 感染疾病的重要靶标。该小鼠模型应有助于进一步了解与慢性疾病相关的病理学,并开发治疗和预防由维尼亚寄生虫引起的利什曼病的方法。
Leishmania (Viannia) organisms are the most prevalent etiologic agents of human cutaneous leishmaniasis in the Americas. Nevertheless, our knowledge of the immunological mechanisms exploited by L. (Viannia) organisms remains limited and the mechanisms underlying disease are not well understood. Here, we report the development of a BALB/c mouse model of L. (V.) panamensis infection that is able to reproduce chronic disease, with persistent infection and clinically evident lesions for over 1 year. The immune response of the mouse resembles that found for L. (V.) panamensis-infected patients with chronic and recurrent lesions, presenting a mixed Th1/Th2 response with the presence of TNF-α, IFN-γ, IL-10 and IL-13. Using immunodeficient mice, the critical role for IL-13 and/or IL-4Rα in determining susceptibility to chronic infection was evident. With the induction of healing in the immunodeficient mice, increases in IFN-γ and IL-17 were found, concomitant with parasite control and elimination. Specifically, increases in CD4+ (but not CD8+) T cells producing IFN-γ were observed. These results suggest that IL-13 represents an important target for disease control of L. (V.) panamensis infection. This murine model should be useful to further understand the pathology associated with chronic disease and to develop methods for the treatment and prevention of leishmaniasis caused by L. (Viannia) parasites.
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