Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT.
Yoav Charpak-AmikamTom LapidusBatya IsaacsonAlexandra Duev-CohenTal LevinsonAdi ElbazFrancesca Levi-SchafferNir OsherovGilad BachrachLois L HoyerMaya KoremRonen Ben-AmiOfer MandelboimPublished in: Nature communications (2022)
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.
Keyphrases
- nk cells
- candida albicans
- immune response
- biofilm formation
- induced apoptosis
- binding protein
- cell wall
- amino acid
- cell cycle
- cell cycle arrest
- peripheral blood
- toll like receptor
- escherichia coli
- endoplasmic reticulum stress
- pseudomonas aeruginosa
- insulin resistance
- cell death
- skeletal muscle
- metabolic syndrome
- dna binding
- protein protein