Phenotypic analysis of natural killer cells in acute dengue infection

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Background: Eady activation of natural killer cells (N Ks) has been shown to associate with protection in dengue m ouse models, and higher N K numbers have been seen in patients with dengue fever (DF) a s opposed to dengue haemorrhagic fever (DHF). Therefore, we set out to investigate the phenotype of N K s in acute dengue infection. Methods: Activating and inhibitory receptors and natural cytotoxicity receptors of N K cells were phenotyped in 25 adult patients with confirmed dengue infection and 10 healthy individuals (HCs). Results: Percentages of N K cells were significantly lower (p=0.0002) in the patients (mean 9.6, SD±3.1) than H C s (mean 4.96, SD+2.7). The C D 56 bright population (CD56B) w as significantly expanded in patients (p=0.0002), especially in those with DF. Expression of N K G 2 D w as higher in both the C D 56 dim and C D 5 6 B N K s in patients with DF when compared to those with DHF. N KG 2A/CD 94 expression w as significantly lower in the C D 56 B in patients (p=0.005), but expression rates were higher in patients with D H F when compared to DF. There w as no difference in NKp30 expression in N K cells from patients and HCs, however, NKp46 expression on N K cells w as lower in patients, especially in the C D 5 6 B group (p=0.007). The N K s of the patients or H C s did not have any detectable expression of NKp44. The C X C R 6 bearing tissue resident N K cells were significantly expanded (p< 0.0001) in patients compared to HCs. Conclusion: Severe forms of dengue appear to associate with reduced expression of activation markers and increased expression of inhibitory markers on N K cells.