Genome-wide expression profiling in malaria infection reveals transcriptional changes associated with lethal and nonlethal outcomes.
High-density oligonucleotide microarrays are widely used to study gene expression in cells exposed to a variety of pathogens. This study addressed the global genome-wide transcriptional activation of genes in hosts infected in vivo, which result in radically different clinical outcomes. We present an analysis of the gene expression profiles that identified a set of host biomarkers which distinguish between lethal and nonlethal blood stage Plasmodium yoelii malaria infections. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. These genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. The transcriptional apparatus that controls gene expression in erythropoiesis was also differentially expressed and regulated the expression of target genes involved in the host's response to malaria anemia. The biological systems approach provides unprecedented opportunities to explore the pathophysiology of host-pathogen interactions in experimental malaria infection and to decipher functionally complex networks of gene and protein interactions.
Schaecher
Kurt
K
Department of Immunology, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910, USA.
Kumar
Sanjai
S
Yadava
Anjali
A
Vahey
Maryanne
M
Ockenhouse
Christian F
CF
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D016678:Genome; D006019:Glycolysis / Q000235:genetics; D008288:Malaria / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology; D010967:Plasmodium yoelii; D014158:Transcription, Genetic / Q000276:immunology