Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria
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Published:2022-07-14
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Musasia Fauzia K., Nkumama Irene N., Frank Roland, Kipkemboi Victor, Schneider Martin, Mwai KennedyORCID, Odera Dennis O., Rosenkranz Micha, Fürle Kristin, Kimani Domitila, Tuju James, Njuguna Patricia, Hamaluba MaingaORCID, Kapulu Melissa C., Wardemann HeddaORCID, Abdi Abdirahman I., Abebe Yonas, Bejon Philip, Billingsley Peter F., Bull Peter C., de Laurent Zaydah, Hoffman Stephen L., James Eric R., Kariuki Silvia, Kimathi Rinter, Kinyanjui Sam, Kivisi Cheryl, Makale Johnstone, Marsh Kevin, Mohammed Khadija Said, Mosobo Moses, Musembi Janet, Musyoki Jennifer, Muthui Michelle, Mwacharo Jedidah, Ndungu Francis, Ngoi Joyce M., Ngoto Omar, Ogutu Bernhards, Olewe Fredrick, Omuoyo Donwilliams, Ong’echa John, Otieno Edward, Shangala Jimmy, Sim Betty Kim Lee, Richie Thomas L., Wambua Juliana, Williams Thomas N., Osier Faith H. A.ORCID,
Abstract
AbstractRing-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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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