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Genetic manipulation of cell line derived reticulocytes enables dissection of host malaria invasion requirements

Author

Listed:
  • Timothy J. Satchwell

    (University of Bristol
    University of Bristol
    National Health Service Blood and Transplant (NHSBT))

  • Katherine E. Wright

    (Imperial College London)

  • Katy L. Haydn-Smith

    (University of Bristol
    University of Bristol
    National Health Service Blood and Transplant (NHSBT))

  • Fernando Sánchez-Román Terán

    (Imperial College London)

  • Pedro L. Moura

    (University of Bristol)

  • Joseph Hawksworth

    (University of Bristol)

  • Jan Frayne

    (University of Bristol
    University of Bristol)

  • Ashley M. Toye

    (University of Bristol
    University of Bristol
    National Health Service Blood and Transplant (NHSBT))

  • Jake Baum

    (Imperial College London)

Abstract

Investigating the role that host erythrocyte proteins play in malaria infection is hampered by the genetic intractability of this anucleate cell. Here we report that reticulocytes derived through in vitro differentiation of an enucleation-competent immortalized erythroblast cell line (BEL-A) support both successful invasion and intracellular development of the malaria parasite Plasmodium falciparum. Using CRISPR-mediated gene knockout and subsequent complementation, we validate an essential role for the erythrocyte receptor basigin in P. falciparum invasion and demonstrate rescue of invasive susceptibility by receptor re-expression. Successful invasion of reticulocytes complemented with a truncated mutant excludes a functional role for the basigin cytoplasmic domain during invasion. Contrastingly, knockout of cyclophilin B, reported to participate in invasion and interact with basigin, did not impact invasive susceptibility of reticulocytes. These data establish the use of reticulocytes derived from immortalized erythroblasts as a powerful model system to explore hypotheses regarding host receptor requirements for P. falciparum invasion.

Suggested Citation

  • Timothy J. Satchwell & Katherine E. Wright & Katy L. Haydn-Smith & Fernando Sánchez-Román Terán & Pedro L. Moura & Joseph Hawksworth & Jan Frayne & Ashley M. Toye & Jake Baum, 2019. "Genetic manipulation of cell line derived reticulocytes enables dissection of host malaria invasion requirements," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11790-w
    DOI: 10.1038/s41467-019-11790-w
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