title: Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.
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.
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.|Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Tuan M
authors: TM
authors: Tran
authors: Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland, USA.
authors: Marcus B
authors: MB
authors: Jones
authors: Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors: Aissata
authors: A
authors: Ongoiba
authors: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Else M
authors: EM
authors: Bijker
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors: Remko
authors: R
authors: Schats
authors: Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland, USA.
authors: Pratap
authors: P
authors: Venepally
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors: Jeff
authors: J
authors: Skinner
authors: Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors: Safiatou
authors: S
authors: Doumbo
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors: Edwin
authors: E
authors: Quinten
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors: Leo G
authors: LG
authors: Visser
authors: Systems Immunology Division, Benaroya Research Institute, Seattle, WA, USA.
authors: Elizabeth
authors: E
authors: Whalen
authors: Systems Immunology Division, Benaroya Research Institute, Seattle, WA, USA.
authors: Scott
authors: S
authors: Presnell
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Elise M
authors: EM
authors: O'Connell
authors: Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors: Kassoum
authors: K
authors: Kayentao
authors: Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors: Ogobara K
authors: OK
authors: Doumbo
authors: Systems Immunology Division, Benaroya Research Institute, Seattle, WA, USA.|Sidra Medical and Research Center, Doha, Qatar.
authors: Damien
authors: D
authors: Chaussabel
authors: Infectious Diseases Group, J. Craig Venter Institute, Bethesda, Maryland, USA.
authors: Hernan
authors: H
authors: Lorenzi
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors: Thomas B
authors: TB
authors: Nutman
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors: Tom H M
authors: TH
authors: Ottenhoff
authors: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors: Mariëlle C
authors: MC
authors: Haks
authors: Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors: Boubacar
authors: B
authors: Traore
authors: Genomic Medicine Group, J. Craig Venter Institute, Rockville, Maryland, USA.
authors: Ewen F
authors: EF
authors: Kirkness
authors: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Robert W
authors: RW
authors: Sauerwein
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors: Peter D
authors: PD
authors: Crompton
mesh_terms: D000293:Adolescent; D016207:Cytokines / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016778:Malaria, Falciparum / Q000097:blood* / Q000276:immunology*; D008297:Male; D008302:Mali; D009426:Netherlands; D010963:Plasmodium falciparum; D016133:Polymerase Chain Reaction; D000075082:Proof of Concept Study; D011446:Prospective Studies; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D055815:Young Adult
chemical_list: D016207:Cytokines