CD56-mediated activation of human natural killer cells is triggered by Aspergillus fumigatus galactosaminogalactan

• Published in: PLoS pathogens 2024-06, Vol.20 (6), p.e1012315
• Main Authors: Heilig, Linda, Natasha, Fariha, Trinks, Nora, Aimanianda, Vishukumar, Wong, Sarah Sze Wah, Fontaine, Thierry, Terpitz, Ulrich, Strobel, Lea, Le Mauff, François, Sheppard, Donald C, Schäuble, Sascha, Kurzai, Oliver, Hünniger, Kerstin, Weiss, Esther, Vargas, Mario, Howell, P Lynne, Panagiotou, Gianni, Wurster, Sebastian, Einsele, Hermann, Loeffler, Juergen
• Format: Article
• Language: English
• Subjects: Activity recognition; Antifungal activity; Aspergillosis; Aspergillosis - immunology; Aspergillosis - microbiology; Aspergillus fumigatus; Aspergillus fumigatus - immunology; Biology and life sciences; Carbohydrates; Care and treatment; CD56 antigen; CD56 Antigen - immunology; CD56 Antigen - metabolism; Cell activation; Cell adhesion molecules; Cell Wall - immunology; Cell Wall - metabolism; Cell walls; Cells; Chemokines; Cytokines; Cytotoxicity; Degranulation; Development and progression; Effector cells; Fungicides; Health aspects; Humans; Immune response; Immune system; Immunocompromised hosts; Immunotherapy; Killer cells; Killer Cells, Natural - immunology; Leukocytes (polymorphonuclear); Life Sciences; Ligands; Lymphocyte Activation - immunology; Medicine and health sciences; Methods; Microbial polysaccharides; Morbidity; Natural killer cells; Pathogens; Physical Sciences; Physiological aspects; Polysaccharides - immunology; Polysaccharides - metabolism; Proteins; Research and Analysis Methods; Virulence
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012315

Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus. However, the underlying cellular mechanisms and the fungal ligand of CD56 have remained unknown. Using purified cell wall components, biochemical treatments, and ger mutants with altered cell wall composition, we herein found that CD56 interacts with the A. fumigatus cell wall carbohydrate galactosaminogalactan (GAG). This interaction induced NK-cell activation, degranulation, and secretion of immune-enhancing chemokines and cytotoxic effectors. Supernatants from GAG-stimulated NK cells elicited antifungal activity and enhanced antifungal effector responses of polymorphonuclear cells. In conclusion, we identified A. fumigatus GAG as a ligand of CD56 on human primary NK cells, stimulating potent antifungal effector responses and activating other immune cells.