Disruption of Nod-like Receptors Alters Inflammatory Response to Infection but Does Not Confer Protection in Experimental Cerebral Malaria
Disruption of Nod-like Receptors Alters Inflammatory Response to Infection but Does Not Confer Protection in Experimental Cerebral Malaria
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DOI：
10.4269/ajtmh.2009.80.718
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发表时间：
2009-05-01
影响因子：
3.3
通讯作者：
Kain, Kevin C.
中科院分区：
文献类型：
--
作者：
Finney, Constance A. M.;Lu, Ziyue;Kain, Kevin C.
有关疟疾感染过程中宿主炎症过程的研究主要集中在Toll样受体、参与先天感知的膜结合受体以及宿主细胞对寄生红细胞的吞噬作用。这是首次研究NOD蛋白在脑型疟疾小鼠模型中的作用。NOD蛋白是参与病原体识别的NOD样受体(NLR)细胞质蛋白家族的成员。在这里，我们发现，与野生型感染动物相比，感染PBA的node1node2(-/-)小鼠在存活率或寄生虫血症方面没有差异。然而，与NLR激活相关的细胞因子水平，特别是那些与NLR激活相关的细胞因子水平，包括白细胞介素1-βKC和单核细胞趋化蛋白-1，以及与疟疾发病相关的蛋白质，如干扰素-伽马，在no1no2(-/-)动物中降低。因此，我们首次证明了NOD蛋白被激活以响应寄生虫，并且它们在调节宿主在疟疾感染过程中的炎症反应中发挥作用。
Research relating to host inflammatory processes during malaria infection has focused on Toll-like receptors, membrane-bound receptors implicated in innate sensing, and phagocytosis of parasitized erythrocytes by host cells. This is the first study to examine the role of Nod proteins, members of the Nod-like receptor (NLR) family of cytoplasmic proteins involved in pathogen recognition, in a murine model of cerebral malaria (Plasmodium berghei ANKA, PbA). Here, we find that nod1nod2(-/-) mice infected with PbA show no difference in survival or parasitemia compared with wild-type infected animals. However, cytokine levels, notably those associated with NLR activation including interleukin (IL)1-beta KC, and MCP-1, and proteins linked to malaria pathogenesis, such as interferon-gamma (IFN-gamma), were decreased in the nod1nod2(-/-) animals. We therefore demonstrate for the first time that Nod proteins are activated in response to parasites, and they play a role in regulating host inflammatory responses during malaria infection.