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Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Transcriptome*; Inflammation/*blood ; Malaria, Falciparum/*blood ; Malaria, Falciparum/*immunology; Adolescent ; Cytokines/immunology ; Female ; Gene Expression Profiling ; Humans ; Male ; Mali ; Netherlands ; Plasmodium falciparum ; Polymerase Chain Reaction ; Proof of Concept Study ; Prospective Studies ; Sequence Analysis, RNA ; Young Adult
    • Abstract:
      Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria.
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    • Grant Information:
      HHSN272200900007C United States AI NIAID NIH HHS; U19 AI110819 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Cytokines)
    • Publication Date:
      Date Created: 20160811 Date Completed: 20180515 Latest Revision: 20181113
    • Publication Date:
      20250114
    • Accession Number:
      PMC4978957
    • Accession Number:
      10.1038/srep31291
    • Accession Number:
      27506615