The blood transcriptome of childhood malaria

Abstract

BackgroundTranscriptomic research of blood cell lineages supports the understanding of distinct features of the immunopathology in human malaria.MethodsWe 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.FindingsOur 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.InterpretationDifferences 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.FundThis 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.

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors

“…Using EPA, we identified similar profiles in experimental systems of inflammatory responses, exercise-induced effects, and pre-clinical models of pain (see Table 2). In terms of inflammatory responses, similar profiles of DGE were found between our survivors with and without PIPN and patients with SARS, (Reghunathan et al, 2005) HIV-1, (Ockenhouse et al, 2005) and malaria (Boldt et al, 2019;Ockenhouse et al, 2006) who were compared to healthy or pre-symptomatic individuals. As noted above, neuroinflammation is thought to play a major role in the development and maintenance of PIPN (Makker, Duffy, 2017, Wang et al, 2012.…”

Understanding P. falciparum Asymptomatic Infections: A Proposition for a Transcriptomic Approach

“…A more recent study in Gabon compared the host transcriptomic profiles between children with uncomplicated, asymptomatic, severe and cerebral malaria and identified 36 genes, among 4,643 transcripts, which are specifically regulated during asymptomatic infections. These genes are involved in nucleotide binding and RNA processing alluding to gene regulation via chromatin remodeling as a potential mode of maintaining asymptomatic infections (6). Chromatin remodeling changes the chromatin architecture, making condensed genomic DNA accessible to the transcription proteins and thereby regulating gene expression.…”

“…At the genomic level, differences in gene expression by the host during host-parasite interactions may account for the various clinical manifestations (5). Specifically, gene pathways that regulate cytokine signaling and complement regulation as well as the production of immunoglobulins have been implicated (6). A strong pro-inflammatory response has been associated with an increased risk of febrile malaria, severe malaria anemia (7) or cerebral malaria (8), while a weak response has been associated with asymptomatic infection (9).…”

Transcriptional blood signatures for active and amphotericin B treated visceral leishmaniasis in India

“…More recently, whole blood transcriptional profiling has been used to study human host responses to protozoan pathogens such as malaria [20, 21] and Chagas disease caused by Trypanosoma cruzi [22, 23]. Expression profiling has also been applied in the context of animal models [24–26] and in human studies [15, 27–29] of the leishmaniases.…”