Genomewide analysis of the host response to malaria in Kenyan children.
Malaria is a global problem, and there is a critical need for further understanding of the disease process. When malarial parasites invade and develop within the bloodstream, they stimulate a profound host response whose main clinical sign is fever. To explore this response, we measured host gene expression in whole blood from Kenyan children hospitalized with either acute malaria or other febrile illnesses. Genomewide analysis of expression identified 2 principal gene-expression profiles related to neutrophil and erythroid activity. In addition to these general acute responses, a third gene-expression profile was associated with host parasitemia; mediators of erythrophagocytosis and cellular stress were notable components of this response. The delineation of subjects on the basis of patterns of gene expression provides a molecular perspective of the host response to malaria and further functional insight into the underlying processes of pathogenesis.
Griffiths
Michael J
MJ
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, UK. griffmj@stanford.edu
Shafi
Mohammed J
MJ
Popper
Stephen J
SJ
Hemingway
Cheryl A
CA
Kortok
Moses M
MM
Wathen
Andrew
A
Rockett
Kirk A
KA
Mott
Richard
R
Levin
Michael
M
Newton
Charles R
CR
Marsh
Kevin
K
Relman
David A
DA
Kwiatkowski
Dominic P
DP
D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007630:Kenya; D007958:Leukocyte Count; D008288:Malaria / Q000097:blood* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D018512:Parasitemia; D010641:Phenotype