Finney Constance A M, Lu Ziyue, LeBourhis Lionel, Philpott Dana J, Kain Kevin C
Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Am J Trop Med Hyg. 2009 May;80(5):718-22.
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 nod-1nod2(-/-) 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.
疟疾感染期间宿主炎症过程的相关研究主要集中在Toll样受体、参与天然免疫传感的膜结合受体以及宿主细胞对被寄生红细胞的吞噬作用上。这是第一项在脑型疟疾（伯氏疟原虫ANKA株，PbA）小鼠模型中研究Nod蛋白（参与病原体识别的胞质蛋白Nod样受体（NLR）家族成员）作用的研究。在此，我们发现感染PbA的nod1nod2(-/-)小鼠与野生型感染动物相比，在存活率或寄生虫血症方面没有差异。然而，细胞因子水平，特别是那些与NLR激活相关的细胞因子，包括白细胞介素（IL）-1β、KC和MCP-1，以及与疟疾发病机制相关的蛋白质，如干扰素-γ（IFN-γ），在nod1nod2(-/-)动物中有所降低。因此，我们首次证明Nod蛋白在对寄生虫的反应中被激活，并且它们在疟疾感染期间调节宿主炎症反应中发挥作用。
