Role of pro-inflammatory cytokine IL-17 in Leishmania pathogenesis and in protective immunity by Leishmania vaccines
Role of pro-inflammatory cytokine IL-17 in Leishmania pathogenesis and in protective immunity by Leishmania vaccines
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DOI：
10.1016/j.cellimm.2016.07.004
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发表时间：
2016-11-01
影响因子：
4.3
通讯作者：
Nakhasi, Hira L.
中科院分区：
文献类型：
--
作者：
Banerjee, Antara;Bhattacharya, Parna;Nakhasi, Hira L.
利什曼原虫发病机制的临床结果包括从活跃的皮肤损伤到致命的内脏传播和严重受损的 T 细胞免疫。众所周知，强烈的 Th1 免疫反应可以预防皮肤疾病，但从之前的研究中可以看出，最常见的是混合 Th1/Th2 免疫反应来预防内脏感染。除 Th1/Th2 细胞因子外，促炎性 IL-17 细胞因子家族在细胞内病原体的清除中也发挥着重要作用。在利什曼原虫引起的皮肤病变中，Th17 细胞产生的 IL-17 会加剧疾病，表明其在发病机制中发挥作用。然而，IL-17 产生细胞在疫苗诱导免疫中的扩增表明了 IL-17 的保护作用。在人内脏利什曼病 (VL) 中，已证明 IL-17 和 IL-22 与防止再次接触利什曼原虫有关，这进一步表明 IL-17 参与了疫苗诱导的保护性免疫。尽管没有针对任何形式的利什曼病的疫苗，但转基因活减毒寄生虫作为候选疫苗的开发被证明是有希望的，因为它们成功地在各种动物模型中诱导了强大的保护性免疫反应。然而，IL-17 产生细胞和 Th17 细胞对这些候选疫苗的反应仍有待探索。在本文中，我们回顾了 IL-17 在利什曼原虫发病机制中的作用以及对疫苗诱导免疫的潜在影响，特别关注活的减毒利什曼原虫寄生虫。由爱思唯尔公司出版
The clinical outcome of Leishmania pathogenesis ranges from active skin lesions to fatal visceral dissemination and severely impaired T cell immunity. It is well established that a strong Th1 immune response is protective against cutaneous forms of the disease, however a mixed Th1/Th2 response is most commonly observed against visceral infections as evident from previous studies. Aside from Th1/Th2 cytokines, the pro-inflammatory IL-17 cytokine family plays an important role in the clearance of intracellular pathogens. In Leishmania induced skin lesions, IL-17 produced by Th17 cells is shown to exacerbate the disease, suggesting a role in pathogenesis. However, a protective role for IL-17 is indicated by the expansion of IL-17 producing cells in vaccine-induced immunity. In human visceral leishmaniasis (VL) it has been demonstrated that IL-17 and IL-22 are associated with protection against re-exposure to Leishmania, which further suggests the involvement of IL-17 in vaccine induced protective immunity. Although there is no vaccine against any form of leishmaniasis, the development of genetically modified live attenuated parasites as vaccine candidates prove to be promising, as they successfully induce a robust protective immune response in various animal models. However, the role of IL-17 producing cells and Th17 cells in response to these vaccine candidates remains unexplored. In this article, we review the role of IL-17 in Leishmania pathogenesis and the potential impact on vaccine induced immunity, with a special focus on live attenuated Leishmania parasites. Published by Elsevier Inc.