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Cytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection

Author

Listed:
  • Raquel Furtado

    (Albert Einstein College of Medicine, Bronx
    RF: BioNTech US)

  • Mahinder Paul

    (Albert Einstein College of Medicine, Bronx)

  • Jinghang Zhang

    (Albert Einstein College of Medicine, Bronx)

  • Joowhan Sung

    (Albert Einstein College of Medicine, Bronx
    Johns Hopkins University School of Medicine)

  • Paul Karell

    (Albert Einstein College of Medicine, Bronx)

  • Ryung S. Kim

    (Albert Einstein College of Medicine, Bronx)

  • Sophie Caillat-Zucman

    (Université de Paris, AP-HP, Hôpital Saint-Louis, Laboratoire d’Immunologie et Histocompatiblité, INSERM UMR976)

  • Li Liang

    (University of California)

  • Philip Felgner

    (University of California)

  • Andy Bauleni

    (Kamuzu University of Health Sciences)

  • Syze Gama

    (Kamuzu University of Health Sciences)

  • Andrea Buchwald

    (University of Maryland School of Medicine)

  • Terrie Taylor

    (Kamuzu University of Health Sciences
    Michigan State University)

  • Karl Seydel

    (Kamuzu University of Health Sciences
    Michigan State University)

  • Miriam Laufer

    (University of Maryland School of Medicine)

  • Fabien Delahaye

    (Albert Einstein College of Medicine, Bronx
    FD: Precision Oncology, Sanofi)

  • Johanna P. Daily

    (Albert Einstein College of Medicine, Bronx
    Albert Einstein College of Medicine, Bronx)

  • Grégoire Lauvau

    (Albert Einstein College of Medicine, Bronx)

Abstract

Clinical immunity against Plasmodium falciparum infection develops in residents of malaria endemic regions, manifesting in reduced clinical symptoms during infection and in protection against severe disease but the mechanisms are not fully understood. Here, we compare the cellular and humoral immune response of clinically immune (0-1 episode over 18 months) and susceptible (at least 3 episodes) during a mild episode of Pf malaria infection in a malaria endemic region of Malawi, by analysing peripheral blood samples using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses. In the clinically immune, we find increased proportions of circulating follicular helper T cells and classical monocytes, while the humoral immune response shows characteristic age-related differences in the protected. Presence of memory CD4+ T cell clones with a strong cytolytic ZEB2+ T helper 1 effector signature, sharing identical T cell receptor clonotypes and recognizing the Pf-derived circumsporozoite protein (CSP) antigen are found in the blood of the Pf-infected participants gaining protection. Moreover, in clinically protected participants, ZEB2+ memory CD4+ T cells express lower level of inhibitory and chemotactic receptors. We thus propose that clonally expanded ZEB2+ CSP-specific cytolytic memory CD4+ Th1 cells may contribute to clinical immunity against the sporozoite and liver-stage Pf malaria.

Suggested Citation

  • Raquel Furtado & Mahinder Paul & Jinghang Zhang & Joowhan Sung & Paul Karell & Ryung S. Kim & Sophie Caillat-Zucman & Li Liang & Philip Felgner & Andy Bauleni & Syze Gama & Andrea Buchwald & Terrie Ta, 2023. "Cytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43376-y
    DOI: 10.1038/s41467-023-43376-y
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    References listed on IDEAS

    as
    1. Lindsey Wu & Lotus L. van den Hoogen & Hannah Slater & Patrick G. T. Walker & Azra C. Ghani & Chris J. Drakeley & Lucy C. Okell, 2015. "Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies," Nature, Nature, vol. 528(7580), pages 86-93, December.
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    4. Freya J I Fowkes & Jack S Richards & Julie A Simpson & James G Beeson, 2010. "The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis," PLOS Medicine, Public Library of Science, vol. 7(1), pages 1-20, January.
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