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Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors

Author

Listed:
  • Xavier Sisquella

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Yifat Ofir-Birin

    (Weizmann Institute of Science)

  • Matthew A. Pimentel

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Lesley Cheng

    (Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
    La Trobe Institute for Molecular Science, La Trobe University)

  • Paula Abou Karam

    (Weizmann Institute of Science)

  • Natália G. Sampaio

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Jocelyn Sietsma Penington

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade)

  • Dympna Connolly

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2)

  • Tal Giladi

    (Weizmann Institute of Science)

  • Benjamin J. Scicluna

    (Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
    La Trobe Institute for Molecular Science, La Trobe University)

  • Robyn A. Sharples

    (Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
    La Trobe Institute for Molecular Science, La Trobe University)

  • Andreea Waltmann

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Dror Avni

    (The Institute of Geographic Medicine & Tropical Diseases and The laboratory for Tropical Diseases Research, Sheba Medical Center)

  • Eli Schwartz

    (The Institute of Geographic Medicine & Tropical Diseases and The laboratory for Tropical Diseases Research, Sheba Medical Center
    Faculty of Medicine, Sackler School of Medicine, Tel Aviv University)

  • Louis Schofield

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street
    Australian Institute of Tropical Health and Medicine, James Cook University)

  • Ziv Porat

    (Flow Cytometry unit, Life Sciences Core Facilities, Weizmann Institute of Science)

  • Diana S. Hansen

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Anthony T. Papenfuss

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Emily M. Eriksson

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade
    Department of Medical Biology, The University of Melbourne, Grattan Street)

  • Motti Gerlic

    (Sackler Faculty of Medicine, Tel Aviv University)

  • Andrew F. Hill

    (Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne
    La Trobe Institute for Molecular Science, La Trobe University)

  • Andrew G. Bowie

    (School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2)

  • Neta Regev-Rudzki

    (Weizmann Institute of Science)

Abstract

STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells is unclear. Here we show that malaria parasites inside red blood cells can engage host cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles (EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human monocytes, P. falciparum DNA is released within the host cell cytosol, leading to STING-dependent DNA sensing. STING subsequently activates the kinase TBK1, which phosphorylates the transcription factor IRF3, causing IRF3 to translocate to the nucleus and induce STING-dependent gene expression. This DNA-sensing pathway may be an important decoy mechanism to promote P. falciparum virulence and thereby may affect future strategies to treat malaria.

Suggested Citation

  • Xavier Sisquella & Yifat Ofir-Birin & Matthew A. Pimentel & Lesley Cheng & Paula Abou Karam & Natália G. Sampaio & Jocelyn Sietsma Penington & Dympna Connolly & Tal Giladi & Benjamin J. Scicluna & Rob, 2017. "Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02083-1
    DOI: 10.1038/s41467-017-02083-1
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