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

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TitleIdentification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.
Publication TypeJournal Article
Year of Publication2018
AuthorsLi, SShun, Ogbomo, H, Mansour, MK, Xiang, RF, Szabo, L, Munro, F, Mukherjee, P, Mariuzza, RA, Amrein, M, Vyas, JM, Robbins, SM, Mody, CH
JournalNat Commun
Volume9
Issue1
Pagination751
Date Published2018 Feb 21
ISSN2041-1723
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.

DOI10.1038/s41467-018-03014-4
Alternate JournalNat Commun
PubMed ID29467448
PubMed Central IDPMC5821813