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

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-Ami, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number2463
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

Funding

FundersFunder number
ISF Israel-China2554/18
Israel Innovation Authority Kamin62615
Israel Science Foundation Moked442-18
MOST-DKFZ3-14931
Israel Cancer Research Fund
German-Israeli Foundation for Scientific Research and Development1412-414.13/2017
Israel Science Foundation
Azrieli Foundation
Ministry of Science and Technology, Israel3-14764

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