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EBioMedicine. 2019 Feb;40:614-625. doi: 10.1016/j.ebiom.2018.12.055. Epub 2019 Jan 10.

The blood transcriptome of childhood malaria.

Author information

1
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Laboratory of Human Molecular Genetics, Department of Genetics, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address: angelicaboldt@gmail.com.
2
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Viet Nam.
3
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.
4
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany.
5
Department of Parasitology, Tropical Medicine and Mycology, University of Libreville, Libreville, Gabon.
6
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.
7
Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany; Center of Medical Research Lambaréné, Lambaréné, Gabon.
8
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. Electronic address: velavan@medizin.uni-tuebingen.de.

Abstract

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:

Cerebral malaria; Gabon; Microarray; Plasmodium falciparum; Severe malaria; Transcriptome; Uncomplicated malaria

PMID:
30638864
PMCID:
PMC6412103
DOI:
10.1016/j.ebiom.2018.12.055
[Indexed for MEDLINE]
Free PMC Article

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