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Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida

Author

Listed:
  • Shu Shun Li

    (University of Calgary
    University of Calgary)

  • Henry Ogbomo

    (University of Calgary
    University of Calgary)

  • Michael K. Mansour

    (Massachusetts General Hospital)

  • Richard F. Xiang

    (University of Calgary
    University of Calgary)

  • Lian Szabo

    (University of Calgary)

  • Fay Munro

    (University of Calgary)

  • Priyanka Mukherjee

    (University of Calgary)

  • Roy A. Mariuzza

    (University of Maryland)

  • Matthias Amrein

    (University of Calgary)

  • Jatin M. Vyas

    (Massachusetts General Hospital)

  • Stephen M. Robbins

    (University of Calgary
    University of Calgary)

  • Christopher H. Mody

    (University of Calgary
    University of Calgary
    University of Calgary)

Abstract

Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging. Through Src Family Kinase signaling, β-1,3-glucan increases expression and clustering of NKp30 at the microbial and NK cell synapse to induce perforin release for fungal cytotoxicity. Rather than blocking the interaction between fungi and NK cells, soluble β-1,3-glucan enhances fungal killing and restores defective cryptococcal killing by NK cells from HIV-positive individuals, implicating β-1,3-glucan to be both an activating ligand and a soluble PAMP that shapes NK cell host immunity.

Suggested Citation

  • Shu Shun Li & Henry Ogbomo & Michael K. Mansour & Richard F. Xiang & Lian Szabo & Fay Munro & Priyanka Mukherjee & Roy A. Mariuzza & Matthias Amrein & Jatin M. Vyas & Stephen M. Robbins & Christopher , 2018. "Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03014-4
    DOI: 10.1038/s41467-018-03014-4
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    Cited by:

    1. Yoav Charpak-Amikam & Mark Kournos & Rebecca Kotzur & Batya Isaacson & Tal Bagad Brenner & Elidet Gomez-Cesar & Ammar Abou-Kandil & Ronen Ben-Ami & Maya Korem & Nadia Guerra & Nir Osherov & Ofer Mande, 2024. "The activating receptor NKG2D is an anti-fungal pattern recognition receptor," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Yoav Charpak-Amikam & Tom Lapidus & Batya Isaacson & Alexandra Duev-Cohen & Tal Levinson & Adi Elbaz & Francesca Levi-Schaffer & Nir Osherov & Gilad Bachrach & Lois L. Hoyer & Maya Korem & Ronen Ben-A, 2022. "Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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