title: 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 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.
authors.affiliation: Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Constance A M
authors.initials: CA
authors.lastname: Finney
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Lu
authors.forename: Lionel
authors.initials: L
authors.lastname: LeBourhis
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation; D016779:Malaria, Cerebral / Q000276:immunology* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D018512:Parasitemia; D010962:Plasmodium berghei
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse