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Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria

Author

Listed:
  • Fauzia K. Musasia

    (Heidelberg University Hospital)

  • Irene N. Nkumama

    (Heidelberg University Hospital
    Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Roland Frank

    (Heidelberg University Hospital)

  • Victor Kipkemboi

    (Heidelberg University Hospital
    Hochschule Rhein-Waal)

  • Martin Schneider

    (German Cancer Research Center)

  • Kennedy Mwai

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
    University of the Witwatersrand)

  • Dennis O. Odera

    (Heidelberg University Hospital
    Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Micha Rosenkranz

    (Heidelberg University Hospital)

  • Kristin Fürle

    (Heidelberg University Hospital)

  • Domitila Kimani

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • James Tuju

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Patricia Njuguna

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Mainga Hamaluba

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Melissa C. Kapulu

    (Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme)

  • Hedda Wardemann

    (German Cancer Research Center)

  • Faith H. A. Osier

    (Heidelberg University Hospital
    Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme
    Imperial College London)

Abstract

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and −140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.

Suggested Citation

  • Fauzia K. Musasia & Irene N. Nkumama & Roland Frank & Victor Kipkemboi & Martin Schneider & Kennedy Mwai & Dennis O. Odera & Micha Rosenkranz & Kristin Fürle & Domitila Kimani & James Tuju & Patricia , 2022. "Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31640-6
    DOI: 10.1038/s41467-022-31640-6
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    1. Janet T. Midega & Dave L. Smith & Ally Olotu & Joseph M. Mwangangi & Joseph G. Nzovu & Juliana Wambua & George Nyangweso & Charles M. Mbogo & George K. Christophides & Kevin Marsh & Philip Bejon, 2012. "Wind direction and proximity to larval sites determines malaria risk in Kilifi District in Kenya," Nature Communications, Nature, vol. 3(1), pages 1-8, January.
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