Host and Parasite Transcriptomic Changes upon Successive <named-content content-type="genus-species">Plasmodium falciparum</named-content> Infections in Early Childhood
Katie R. Bradwell,
Drissa Coulibaly,
Abdoulaye K. Koné,
Matthew B. Laurens,
Ahmadou Dembélé,
Youssouf Tolo,
Karim Traoré,
Amadou Niangaly,
Andrea A. Berry,
Bourema Kouriba,
Christopher V. Plowe,
Ogobara K. Doumbo,
Kirsten E. Lyke,
Shannon Takala-Harrison,
Mahamadou A. Thera,
Mark A. Travassos,
David Serre
Affiliations
Katie R. Bradwell
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Drissa Coulibaly
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Abdoulaye K. Koné
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Matthew B. Laurens
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Ahmadou Dembélé
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Youssouf Tolo
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Karim Traoré
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Amadou Niangaly
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Andrea A. Berry
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Bourema Kouriba
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Christopher V. Plowe
Duke Global Health Institute, Duke University, Durham, North Carolina, USA
Ogobara K. Doumbo
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Kirsten E. Lyke
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Shannon Takala-Harrison
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Mahamadou A. Thera
Malaria Research and Training Center, University of Science, Techniques and Technologies, Bamako, Mali
Mark A. Travassos
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
David Serre
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
ABSTRACT Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq). IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.
