title: Transcriptional profiling reveals suppressed erythropoiesis, up-regulated glycolysis, and interferon-associated responses in murine malaria.
abstract: The primary pathophysiological events contributing to fatal malaria are the cerebral syndrome, anemia, and lactic acidosis. The molecular basis of each event has been unclear. In the present study, microarray analysis of murine transcriptional responses during the development of severe disease revealed temporal, organ-specific, and pathway-specific patterns. More than 400 genes in the brain and 600 genes in the spleen displayed transcriptional changes. Dominant patterns revealed strongly suppressed erythropoiesis, starting early during infection, and highly up-regulated transcription of genes that control host glycolysis, including lactate dehydrogenase. The latter presents a mechanism that may contribute to metabolic acidosis. No evidence for hypoxia-mediated regulation of these events was observed. Interferon-regulated gene transcripts dominated the inflammatory response to cytokines. These results demonstrate previously unknown transcriptional changes in the host that may underlie the development of malarial syndromes, such as anemia and metabolic dysregulation, and increase the utility of murine models in investigation of basic malarial pathogenesis.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, IG Royal Parade, Parkville, Victoria, Australia.
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Sexton
authors.forename: Robert T
authors.initials: RT
authors.lastname: Good
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.forename: Marthe C
authors.initials: MC
authors.lastname: D'Ombrain
authors.forename: Lynn
authors.initials: L
authors.lastname: Buckingham
authors.forename: Ken
authors.initials: K
authors.lastname: Simpson
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D008288:Malaria / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010962:Plasmodium berghei; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D007371:Interferon-gamma; D004247:DNA