Short report: disruption of Nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria

Abstract. 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 pro-teins 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-β, KC, and MCP-1, and proteins linked to malaria pathogenesis, such as interferon-γ (IFN-γ), 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. Severe malaria can present as a variety of clinical syndromes, including both severe malarial anemia and cerebral malaria (CM), to which the majority of deaths are attributable. 1 Plasmodium berghei ANKA infection represents an experi-mental model of CM, with associated neurologic symptoms. 2,3 Mice susceptible to this pathogen (e.g., C57BL/6 strain) suc