TY - JOUR
T1 - NK Cell Recognition of Candida glabrata through Binding of NKp46 and NCR1 to Fungal Ligands Epa1, Epa6, and Epa7
AU - Vitenshtein, Alon
AU - Charpak-Amikam, Yoav
AU - Yamin, Rachel
AU - Bauman, Yoav
AU - Isaacson, Batya
AU - Stein, Natan
AU - Berhani, Orit
AU - Dassa, Liat
AU - Gamliel, Moriya
AU - Gur, Chamutal
AU - Glasner, Ariella
AU - Gomez, Carlos
AU - Ben-Ami, Ronen
AU - Osherov, Nir
AU - Cormack, Brendan P.
AU - Mandelboim, Ofer
N1 - Funding Information:
This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement number 320473-BacNK and by the NIH (5RO1AI046223). Further support came from the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation and by the I-Core on Chromatin and RNA in Gene Regulation, the GIF foundation, the Lewis family foundation, the ICRF professorship grant, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). We thank David Smith and Richard Cummings for the glycan array screening carried out by the Consortium for Functional Glycomics, which is supported by NIH grants GM62116 and GM098791.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/12
Y1 - 2016/10/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2016.09.008
DO - 10.1016/j.chom.2016.09.008
M3 - Article
C2 - 27736647
AN - SCOPUS:84992411684
SN - 1931-3128
VL - 20
SP - 527
EP - 534
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -