Human Gene Expression in Uncomplicated Plasmodium falciparum Malaria.
To examine human gene expression during uncomplicated P. falciparum malaria, we obtained three samples (acute illness, treatment, and recovery) from 10 subjects and utilized each subject's recovery sample as their baseline. At the time of acute illness (day 1), subjects had upregulation of innate immune response, cytokine, and inflammation-related genes (IL-1β, IL-6, TNF, and IFN-γ), which was more frequent with parasitemias >100,000 per μL and body temperatures ≥ 39°C. Apoptosis-related genes (Fas, BAX, and TP53) were upregulated acutely and for several days thereafter (days 1-3). In contrast, the expression of immune-modulatory (transcription factor 7, HLV-DOA, and CD6) and apoptosis inhibitory (c-myc, caspase 8, and Fas Ligand G) genes was downregulated initially and returned to normal with clinical recovery (days 7-10). These results indicate that the innate immune response, cytokine, and apoptosis pathways are upregulated acutely in uncomplicated malaria with concomitant downregulation of immune-modulatory and apoptosis inhibitory genes.
Center for Infectious Diseases, Tulane University Health Sciences Center, New Orleans, LA 70112, USA ; Department of Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA ; Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
James M
JM
Colborn
Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA 70112, USA ; Department of Biology, University of Mary Hardin-Baylor, 900 College Street, Box 8432, Belton, TX 76513, USA.
Joni H
JH
Ylöstalo
The Faculties of Science, Technology, Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, Mali.
Ousmane A
OA
Koita
The Faculties of Science, Technology, Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, Mali ; Institute of Microbiology, University of Lausanne, 1011 Lausanne, Switzerland.
Ousmane H
OH
Cissé
Center for Infectious Diseases, Tulane University Health Sciences Center, New Orleans, LA 70112, USA ; Department of Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA ; Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Donald J
DJ
Krogstad
D000293:Adolescent; D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D019295:Computational Biology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D008297:Male; D018512:Parasitemia; D015203:Reproducibility of Results; D013696:Temperature