srep41722.pdf (6.28 MB)
Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria
journal contributionposted on 2020-10-19, 14:41 authored by Jing Wen Lin, Jan Sodenkamp, Deirdre Cunningham, Katrien Deroost, Tshibuayi Christine Tshitenge, Sarah McLaughlin, Tracey J Lamb, Bradley Spencer-Dene, Caroline Hosking, Jai Ramesar, Chris J Janse, Christine Graham, Anne O'Garra, Jean Langhorne
The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.
AnimalsCluster AnalysisDisease Models, AnimalErythrocytesGene Expression ProfilingHost-Parasite InteractionsLife Cycle StagesMalariaMiceMice, Inbred C57BLNeutrophil InfiltrationOrgan SpecificityPlasmodiumPlasmodium chabaudiPlatelet AggregationTranscriptomeVirulenceLanghorne FC001101O'Garra FC001126HPBRF-ackHTS-ackFC-ackLM-ack0601 Biochemistry and Cell Biology0299 Other Physical Sciences