Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania
Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania
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DOI：
10.1038/nm.3221
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发表时间：
2013-07-01
期刊：
影响因子：
82.9
通讯作者：
Zamboni, Dario S.
中科院分区：
文献类型：
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作者：
Lima-Junior, Djalma S.;Costa, Diego L.;Zamboni, Dario S.
利什曼原虫属寄生虫是人类利什曼病的病原体，这种疾病在全球范围内影响着1200多万人。这些寄生虫在巨噬细胞内复制，宿主抵抗的主要机制涉及一氧化氮(NO)的产生。在本研究中，我们通过感染亚马逊利什曼原虫、巴西利什曼原虫和婴儿查加西利什曼原虫感染炎性小体缺陷小鼠，证明了Nlrp3炎症体被激活是对利什曼原虫感染的反应，并且对于限制寄生虫在巨噬细胞和体内的复制具有重要作用。炎症小体驱动的白介素1β(IL-1β)的产生促进了宿主对感染的抵抗，因为通过IL-1受体(IL-1R)和MyD88的信号是触发诱导型一氧化氮合酶(NOS2)介导的NO产生的必要条件和充分条件。在这篇手稿中，我们确定了宿主对利什曼原虫抗性的一个主要信号平台。并描述利什曼原虫诱导NO产生的分子机制。
Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflammasome is activated in response to Leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as demonstrated through the infection of inflammasome-deficient mice with Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum chagasi. Inflammasome-driven interleukin-1 beta (IL-1 beta) production facilitated host resistance to infection, as signaling through IL-1 receptor (IL-1R) and MyD88 was necessary and sufficient to trigger inducible nitric oxide synthase (NOS2)-mediated production of NO. In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania-induced NO production.