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

Tuan M. Tran, Marcus B. Jones, Aissata Ongoiba, Else M. Bijker, Remko Schats, Pratap Venepally, Jeff Skinner, Safiatou Doumbo, Edwin Quinten, Leo G. Visser, Elizabeth Whalen, Scott Presnell, Elise M. O'Connell, Kassoum Kayentao, Ogobara K. Doumbo, Damien Chaussabel, Hernan Lorenzi, Thomas B. Nutman, Tom H.M. Ottenhoff, Mariëlle C. HaksBoubacar Traore, Ewen F. Kirkness, Robert W. Sauerwein, Peter D. Crompton

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28 Scopus citations

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.

Original languageEnglish (US)
Article number31291
JournalScientific reports
Volume6
DOIs
StatePublished - Oct 8 2016

ASJC Scopus subject areas

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    Tran, T. M., Jones, M. B., Ongoiba, A., Bijker, E. M., Schats, R., Venepally, P., Skinner, J., Doumbo, S., Quinten, E., Visser, L. G., Whalen, E., Presnell, S., O'Connell, E. M., Kayentao, K., Doumbo, O. K., Chaussabel, D., Lorenzi, H., Nutman, T. B., Ottenhoff, T. H. M., ... Crompton, P. D. (2016). Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria. Scientific reports, 6, [31291]. https://doi.org/10.1038/srep31291