Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida

Nat Commun. 2018 Feb 21;9(1):751. doi: 10.1038/s41467-018-03014-4.


Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging. Through Src Family Kinase signaling, β-1,3-glucan increases expression and clustering of NKp30 at the microbial and NK cell synapse to induce perforin release for fungal cytotoxicity. Rather than blocking the interaction between fungi and NK cells, soluble β-1,3-glucan enhances fungal killing and restores defective cryptococcal killing by NK cells from HIV-positive individuals, implicating β-1,3-glucan to be both an activating ligand and a soluble PAMP that shapes NK cell host immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / immunology*
  • Cell Line
  • Cell Polarity / immunology
  • Cryptococcus neoformans / immunology*
  • Cytoplasmic Granules / immunology
  • Cytotoxicity, Immunologic
  • HIV Infections / immunology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunological Synapses / immunology
  • Killer Cells, Natural / immunology*
  • Ligands
  • Microscopy, Atomic Force
  • Natural Cytotoxicity Triggering Receptor 3 / immunology
  • Pathogen-Associated Molecular Pattern Molecules / immunology*
  • Perforin / immunology
  • Recombinant Proteins / immunology
  • Solubility
  • beta-Glucans / immunology


  • Ligands
  • NCR3 protein, human
  • Natural Cytotoxicity Triggering Receptor 3
  • Pathogen-Associated Molecular Pattern Molecules
  • Recombinant Proteins
  • beta-Glucans
  • Perforin
  • beta-1,3-glucan