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Human Cytomegalovirus Drives Epigenetic Imprinting of the Locus in NKG2C Natural Killer Cells


Upon viral infection, the innate interferon (IFN)-γ producing Natural Killer (NK) cells provide fast, but short-term protection, while adaptive T cells confer delayed, but long-lasting immunity. Once acquired, effector properties remain stably imprinted in the T cell memory progeny. Recently, it was shown that human cytomegalovirus (HCMV) infection can shape the human NK cell repertoire and drive the generation and maintenance of NK cell expansions, which express the activating receptor CD94/NKG2C and have been described as memory-like NK cells. However, the molecular mechanisms underlying NK cell adaptive properties driven by HCMV infection have not been completely defined. In this study, we identify epigenetic imprinting of the IFNG locus as selective hallmark and crucial mechanism driving strong and stable IFN-γ expression in HCMV-specific NK cell expansions, thus providing a molecular basis for the regulation of adaptive features in innate cells.


Vyšlo v časopise: Human Cytomegalovirus Drives Epigenetic Imprinting of the Locus in NKG2C Natural Killer Cells. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004441
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004441

Souhrn

Upon viral infection, the innate interferon (IFN)-γ producing Natural Killer (NK) cells provide fast, but short-term protection, while adaptive T cells confer delayed, but long-lasting immunity. Once acquired, effector properties remain stably imprinted in the T cell memory progeny. Recently, it was shown that human cytomegalovirus (HCMV) infection can shape the human NK cell repertoire and drive the generation and maintenance of NK cell expansions, which express the activating receptor CD94/NKG2C and have been described as memory-like NK cells. However, the molecular mechanisms underlying NK cell adaptive properties driven by HCMV infection have not been completely defined. In this study, we identify epigenetic imprinting of the IFNG locus as selective hallmark and crucial mechanism driving strong and stable IFN-γ expression in HCMV-specific NK cell expansions, thus providing a molecular basis for the regulation of adaptive features in innate cells.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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