title: NK Cell Recognition of Candida glabrata through Binding of NKp46 and NCR1 to Fungal Ligands Epa1, Epa6, and Epa7.
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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Vitenshtein
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Charpak-Amikam
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Bauman
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Isaacson
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Natan
authors.initials: N
authors.lastname: Stein
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Berhani
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Dassa
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Moriya
authors.initials: M
authors.lastname: Gamliel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez
authors.affiliation: Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, 6423906 Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, 39040 Tel Aviv, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Ben-Ami
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 39040 Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: bcormack@jhmi.edu.
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Cormack
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine (IMRIC), The Hebrew University Hadassah Medical School, 91120 Jerusalem, Israel. Electronic address: oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D041221:Candida glabrata / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D005656:Fungal Proteins; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse