NK Cell Recognition of Candida glabrata through Binding of NKp46 and NCR1 to Fungal Ligands Epa1, Epa6, and Epa7

Alon Vitenshtein, Yoav Charpak-Amikam, Rachel Yamin, Yoav Bauman, Batya Isaacson, Natan Stein, Orit Berhani, Liat Dassa, Moriya Gamliel, Chamutal Gur, Ariella Glasner, Carlos Gomez, Ronen Ben-Ami, Nir Osherov, Brendan P. Cormack*, Ofer Mandelboim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Natural killer (NK) cells form an important arm of the innate immune system and function to combat a wide range of invading pathogens, ranging from viruses to bacteria. However, the means by which NK cells accomplish recognition of pathogens with a limited repertoire of receptors remain largely unknown. In the current study, we describe the recognition of an emerging fungal pathogen, Candida glabrata, by the human NK cytotoxic receptor NKp46 and its mouse ortholog, NCR1. Using NCR1 knockout mice, we observed that this receptor-mediated recognition was crucial for controlling C. glabrata infection in vitro and in vivo. Finally, we delineated the fungal ligands to be the C. glabrata adhesins Epa1, Epa6, and Epa7 and demonstrated that clearance of systemic C. glabrata infections in vivo depends on their recognition by NCR1. As NKp46 and NCR1 have been previously shown to bind viral adhesion receptors, we speculate that NKp46/NCR1 may be a novel type of pattern recognition receptor.

Original languageEnglish
Pages (from-to)527-534
Number of pages8
JournalCell Host and Microbe
Volume20
Issue number4
DOIs
StatePublished - 12 Oct 2016

Funding

FundersFunder number
GIF Foundation
Helmholtz Israel
I-Core on Chromatin
Lewis Family Foundation
National Institutes of Health5RO1AI046223
National Institute of General Medical SciencesU54GM062116
Israel Cancer Research Fund
European Research Council320473-BacNK
Rosetrees TrustGM098791
Israel Science Foundation
Seventh Framework ProgrammeFP/2007-2013
Planning and Budgeting Committee of the Council for Higher Education of Israel

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