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Malaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin

Author

Listed:
  • Hardik Patel

    (Seattle Children’s Research Institute)

  • Nana K. Minkah

    (Seattle Children’s Research Institute
    University of Washington)

  • Sudhir Kumar

    (Seattle Children’s Research Institute)

  • Gigliola Zanghi

    (Seattle Children’s Research Institute)

  • Antonino Schepis

    (Seattle Children’s Research Institute)

  • Debashree Goswami

    (Seattle Children’s Research Institute)

  • Janna Armstrong

    (Seattle Children’s Research Institute)

  • Biley A. Abatiyow

    (Seattle Children’s Research Institute)

  • Will Betz

    (Seattle Children’s Research Institute)

  • Laura Reynolds

    (Seattle Children’s Research Institute)

  • Nelly Camargo

    (Seattle Children’s Research Institute)

  • Amina A. Sheikh

    (Seattle Children’s Research Institute)

  • Stefan H. I. Kappe

    (Seattle Children’s Research Institute
    University of Washington
    University of Washington)

Abstract

Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these stages impact each other via perturbation of host responses, and this influences the outcome of natural infection. We sought to understand whether the parasite stage interplay would affect live-attenuated whole parasite vaccination, since the efficacy of whole parasite vaccines strongly correlates with their extend of development in the liver. We thus investigated the impact of BS infection on LS development of genetically attenuated and wildtype parasites in female rodent malaria models and observed that for both, LS infection suffered severe suppression during concurrent BS infection. Strikingly and in contrast to previously published studies, we find that the BS-induced iron-regulating hormone hepcidin is not mediating suppression of LS development. Instead, we demonstrate that BS-induced host interferons are the main mediators of LS developmental suppression. The type of interferon involved depended on the BS-causing parasite species. Our study provides important mechanistic insights into the BS-mediated suppression of LS development. This has direct implications for understanding the outcomes of live-attenuated Plasmodium parasite vaccination in malaria-endemic areas and might impact the epidemiology of natural malaria infection.

Suggested Citation

  • Hardik Patel & Nana K. Minkah & Sudhir Kumar & Gigliola Zanghi & Antonino Schepis & Debashree Goswami & Janna Armstrong & Biley A. Abatiyow & Will Betz & Laura Reynolds & Nelly Camargo & Amina A. Shei, 2024. "Malaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46270-3
    DOI: 10.1038/s41467-024-46270-3
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    References listed on IDEAS

    as
    1. Benjamin Mordmüller & Güzin Surat & Heimo Lagler & Sumana Chakravarty & Andrew S. Ishizuka & Albert Lalremruata & Markus Gmeiner & Joseph J. Campo & Meral Esen & Adam J. Ruben & Jana Held & Carlos Lam, 2017. "Sterile protection against human malaria by chemoattenuated PfSPZ vaccine," Nature, Nature, vol. 542(7642), pages 445-449, February.
    2. Nana K. Minkah & Brandon K. Wilder & Amina A. Sheikh & Thomas Martinson & Lisa Wegmair & Ashley M. Vaughan & Stefan H. I. Kappe, 2019. "Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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