Abstract
AbstractCandida 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.
Funder
Israel Science Foundation
Israel Cancer Research Fund
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference63 articles.
1. Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L. & Kullberg, B. J. Invasive candidiasis. Nat. Rev. Dis. Prim. 4, 1–20 (2018).
2. Noble, S. M., Gianetti, B. A. & Witchley, J. N. Candida albicans cell-type switching and functional plasticity in the mammalian host. Nat. Rev. Microbiol. 15, 96–108 (2017).
3. Netea, M. G., Joosten, L. A., van der Meer, J. W., Kullberg, B. J. & van de Veerdonk, F. L. Immune defence against Candida fungal infections. Nat. Rev. Immunol. 15, 630–642 (2015).
4. Bacher, P. et al. Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176, 1340–1355.e15 (2019).
5. Shao, T.-Y. et al. Commensal Candida albicans positively calibrates systemic Th17 immunological responses. Cell Host Microbe 25, 404–417.e6 (2019).
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献