Mass Cytometry Analysis of the NK Cell Receptor-Ligand Repertoire Reveals Unique Differences between Dengue-Infected Children and Adults

• Published in: ImmunoHorizons 2020-10, Vol.4 (10), p.634-647
• Main Authors: McKechnie, Julia L, Beltrán, Davis, Ferreira, Anne-Maud M, Vergara, Rosemary, Saenz, Lisseth, Vergara, Ofelina, Estripeaut, Dora, Araúz, Ana B, Simpson, Laura J, Holmes, Susan, López-Vergès, Sandra, Blish, Catherine A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - immunology; Biomarkers; CD57 Antigens - immunology; Child; Child, Preschool; Dengue - blood; Dengue - immunology; Fas Ligand Protein - metabolism; Female; Flow Cytometry - methods; Humans; Killer Cells, Natural - immunology; Lymphocyte Activation; Male; Middle Aged; Perforin - metabolism; Receptors, Natural Killer Cell - immunology; Staining and Labeling; Young Adult
• ISSN: 2573-7732; 2573-7732
• DOI: 10.4049/immunohorizons.2000074

Dengue virus (DENV) is a significant cause of morbidity in many regions of the world, with children at the greatest risk of developing severe dengue. NK cells, characterized by their ability to rapidly recognize and kill virally infected cells, are activated during acute DENV infection. However, their role in viral clearance versus pathogenesis has not been fully elucidated. Our goal was to profile the NK cell receptor-ligand repertoire to provide further insight into the function of NK cells during pediatric and adult DENV infection. We used mass cytometry to phenotype isolate NK cells and PBMCs from a cohort of DENV-infected children and adults. Using unsupervised clustering, we found that pediatric DENV infection leads to a decrease in total NK cell frequency with a reduction in the percentage of CD56 CD38 NK cells and an increase in the percentage of CD56 perforin NK cells. No such changes were observed in adults. Next, we identified markers predictive of DENV infection using a differential state test. In adults, NK cell expression of activation markers, including CD69, perforin, and Fas-L, and myeloid cell expression of activating NK cell ligands, namely Fas, were predictive of infection. In contrast, increased NK cell expression of the maturation marker CD57 and myeloid cell expression of inhibitory ligands, such as HLA class I molecules, were predictive of pediatric DENV infection. These findings suggest that acute pediatric DENV infection may result in diminished NK cell activation, which could contribute to enhanced pathogenesis and disease severity.