Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04685-9
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Funding
- International Research Training Group 1273 - German Research Foundation (DFG)
- DFG [738, 900]
- Deutsches Zentrum fur Infektions-forschung (DZIF)
- German Liver Foundation
- Swedish Research Council
- Swedish Cancer Society
- Swedish Foundation for Strategic Research
- Swedish Society for Medical Research
- Cancer Research Foundations of Radiumhemmet
- Knut and Alice Wallenberg Foundation
- Novo Nordisk Foundation
- Ake Wiberg's Foundation
- Center for Innovative Medicine at Karolinska Institutet
- Stockholm County Council
- Karolinska Institutet
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Diversity is a central requirement for the immune system's capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
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