The blood transcriptome of childhood malariaResearch in context
Angelica B.W. Boldt,
Hoang van Tong,
Martin P. Grobusch,
Yvonne Kalmbach,
Arnaud Dzeing Ella,
Maryvonne Kombila,
Christian G. Meyer,
Jürgen F.J. Kun,
Peter G. Kremsner,
Thirumalaisamy P. Velavan
Affiliations
Angelica B.W. Boldt
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Laboratory of Human Molecular Genetics, Department of Genetics, Universidade Federal do Paraná, Curitiba, Brazil; Correspondence to: A. B. W. Boldt, Departamento de Genética, Universidade Federal do Paraná, Caixa Postal 19071, 81531-980 Curitiba, Brasil.
Hoang van Tong
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Viet Nam
Martin P. Grobusch
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Center of Medical Research Lambaréné, Lambaréné, Gabon; Center of Travel Medicine and Tropical Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, Amsterdam University Medical Centers, the Netherlands
Yvonne Kalmbach
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany
Arnaud Dzeing Ella
Department of Parasitology, Tropical Medicine and Mycology, University of Libreville, Libreville, Gabon
Maryvonne Kombila
Department of Parasitology, Tropical Medicine and Mycology, University of Libreville, Libreville, Gabon
Christian G. Meyer
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Viet Nam; Duy Tan University, Da Nang, Viet Nam
Jürgen F.J. Kun
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany
Peter G. Kremsner
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Center of Medical Research Lambaréné, Lambaréné, Gabon
Thirumalaisamy P. Velavan
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Viet Nam; Duy Tan University, Da Nang, Viet Nam; Correspondence to: T. P Velavan, Institute of Tropical Medicine, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany.
Background: Transcriptomic research of blood cell lineages supports the understanding of distinct features of the immunopathology in human malaria. Methods: We used microarray hybridization, validated by real-time RT-PCR to analyze whole blood gene expression in healthy Gabonese children and children with various conditions of Plasmodium falciparum infection, including i) asymptomatic infection, ii) uncomplicated malaria, iii) malaria associated with severe anemia and iv) cerebral malaria. Findings: Our data indicate that the expression profile of 22 genes significantly differed among the investigated groups. Immunoglobulin production, complement regulation and IFN beta signaling, in particular IRF7 and ISRE binding signatures in the corresponding genes, were most conspicuous. Down-regulation in cerebral malaria seems to rely on AhRF, GABP and HIF1 hypoxia transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia, and negatively with hemoglobin concentrations. Interpretation: Differences in gene expression profile reflect distinct immunopathological mechanisms of P. falciparum infection. They emerge as potential prognostic markers for early therapeutic measures and need to be validated further. Fund: This work was supported by a grant of the NGFN (Nationales Genomforschungsnetz 01GS0114) and by a CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) PhD scholarship for A. B. W. Boldt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Keywords: Uncomplicated malaria, Severe malaria, Cerebral malaria, Transcriptome, Plasmodium falciparum, Microarray, Gabon
