TY - JOUR
T1 - Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT
AU - Charpak-Amikam, Yoav
AU - Lapidus, Tom
AU - Isaacson, Batya
AU - Duev-Cohen, Alexandra
AU - Levinson, Tal
AU - Elbaz, Adi
AU - Levi-Schaffer, Francesca
AU - Osherov, Nir
AU - Bachrach, Gilad
AU - Hoyer, Lois L.
AU - Korem, Maya
AU - Ben-Ami, Ronen
AU - Mandelboim, Ofer
N1 - The authors would like to thank Prof. Brendan Cormack for supplying critical fungal strains. We would like to also thank the Fungal Genomic Stock Center (FGSC) for providing the C. albicans deletion library. Y.C.A. is supported by the Azrieli Foundation. This work was supported by the following grants awarded to O.M.: the Israel Innovation Authority Kamin grant 62615, the German-Israeli Foundation for Scientific Research and Development grant 1412-414.13/2017, the ICRF professorship grant, the ISF Israel-China grant 2554/18, the MOST-DKFZ grant 3-14931, and the Ministry of Science and Technology grant 3-14764 and by the Israel Science Foundation Moked grant 442-18 awarded to O.M., F.L.S., N.O., G.B. and R.B.A.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30087-z
DO - 10.1038/s41467-022-30087-z
M3 - Article
C2 - 35513379
AN - SCOPUS:85129446339
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2463
ER -