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Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT

Author

Listed:
  • Yoav Charpak-Amikam

    (Hebrew University Medical School, IMRIC)

  • Tom Lapidus

    (Hebrew University Medical School, IMRIC)

  • Batya Isaacson

    (Hebrew University Medical School, IMRIC)

  • Alexandra Duev-Cohen

    (Hebrew University Medical School, IMRIC)

  • Tal Levinson

    (Tel Aviv University)

  • Adi Elbaz

    (Hebrew University of Jerusalem)

  • Francesca Levi-Schaffer

    (Hebrew University of Jerusalem)

  • Nir Osherov

    (Tel-Aviv University, Ramat-Aviv)

  • Gilad Bachrach

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Lois L. Hoyer

    (University of Illinois at Urbana-Champaign)

  • Maya Korem

    (Hadassah-Hebrew University Medical Center)

  • Ronen Ben-Ami

    (Tel Aviv University)

  • Ofer Mandelboim

    (Hebrew University Medical School, IMRIC)

Abstract

Candida albicans is the most common fungal pathogen and a prevalent cause of deadly bloodstream infections. Better understanding of the immune response against it, and the ways by which it evades immunity, are crucial for developing new therapeutics against it. Natural Killer (NK) cells are innate lymphocytes best known for their role against viruses and tumors. In recent years it became clear that NK cells also play an important role in anti-fungal immunity. Here we show that while NK cells recognize and eliminate C. albicans, the fungal cells inhibit NK cells by manipulating the immune checkpoint receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) in both humans and mice. We identify the responsible fungal ligands as members of the Als (Agglutinin-Like Sequences) protein family. Furthermore, we show that blocking this interaction using immunotherapy with a TIGIT-blocking antibody can re-establish anti-Candida immunity and serve as a potential therapeutic tool.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30087-z
    DOI: 10.1038/s41467-022-30087-z
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    References listed on IDEAS

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    1. Michelle Schorer & Nikolas Rakebrandt & Katharina Lambert & Annika Hunziker & Katharina Pallmer & Annette Oxenius & Anja Kipar & Silke Stertz & Nicole Joller, 2020. "TIGIT limits immune pathology during viral infections," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Ofer Mandelboim & Niva Lieberman & Marianna Lev & Lada Paul & Tal I. Arnon & Yuri Bushkin & Daniel M. Davis & Jack L. Strominger & Jonathan W. Yewdell & Angel Porgador, 2001. "Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells," Nature, Nature, vol. 409(6823), pages 1055-1060, February.
    3. 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.
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