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Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites

Author

Listed:
  • Nana K. Minkah

    (Seattle Children’s Research Institute)

  • Brandon K. Wilder

    (Seattle Children’s Research Institute
    Oregon Health and Science University)

  • Amina A. Sheikh

    (Seattle Children’s Research Institute)

  • Thomas Martinson

    (Seattle Children’s Research Institute
    Oregon Health and Science University)

  • Lisa Wegmair

    (Seattle Children’s Research Institute
    Santis GmbH/Astrazeneca)

  • Ashley M. Vaughan

    (Seattle Children’s Research Institute)

  • Stefan H. I. Kappe

    (Seattle Children’s Research Institute
    University of Washington)

Abstract

Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11819-0
    DOI: 10.1038/s41467-019-11819-0
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    Cited by:

    1. 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.

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