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

Shu Shun Li, Henry Ogbomo, Michael K. Mansour, Richard F. Xiang, Lian Szabo, Fay Munro, Priyanka Mukherjee, Roy A. Mariuzza, Matthias Amrein, Jatin M. Vyas, Stephen M. Robbins and Christopher H. Mody ()
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Shu Shun Li: University of Calgary
Henry Ogbomo: University of Calgary
Michael K. Mansour: Massachusetts General Hospital
Richard F. Xiang: University of Calgary
Lian Szabo: University of Calgary
Fay Munro: University of Calgary
Priyanka Mukherjee: University of Calgary
Roy A. Mariuzza: University of Maryland
Matthias Amrein: University of Calgary
Jatin M. Vyas: Massachusetts General Hospital
Stephen M. Robbins: University of Calgary
Christopher H. Mody: University of Calgary

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03014-4

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