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Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells

Author

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  • Carmen Rožmanić

    (University of Rijeka)

  • Berislav Lisnić

    (University of Rijeka)

  • Marina Pribanić Matešić

    (University of Rijeka)

  • Andrea Mihalić

    (University of Rijeka)

  • Lea Hiršl

    (University of Rijeka)

  • Eugene Park

    (Washington University School of Medicine)

  • Ana Lesac Brizić

    (University of Rijeka)

  • Daniela Indenbirken

    (Heinrich Pette Institute, Leibniz Institute for Experimental Virology)

  • Ina Viduka

    (University of Rijeka, Faculty of Medicine)

  • Marina Šantić

    (University of Rijeka, Faculty of Medicine)

  • Barbara Adler

    (Max von Pettenkofer Institute & Gene Center, Virology, Faculty of Medicine, LMU Munich)

  • Wayne M. Yokoyama

    (Washington University School of Medicine)

  • Astrid Krmpotić

    (Faculty of Medicine, University of Rijeka)

  • Vanda Juranić Lisnić

    (University of Rijeka)

  • Stipan Jonjić

    (University of Rijeka)

  • Ilija Brizić

    (University of Rijeka)

Abstract

Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA Ifng-as1 expression. Moreover, the bone marrow’s capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.

Suggested Citation

  • Carmen Rožmanić & Berislav Lisnić & Marina Pribanić Matešić & Andrea Mihalić & Lea Hiršl & Eugene Park & Ana Lesac Brizić & Daniela Indenbirken & Ina Viduka & Marina Šantić & Barbara Adler & Wayne M. , 2023. "Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42182-w
    DOI: 10.1038/s41467-023-42182-w
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    References listed on IDEAS

    as
    1. Joseph C. Sun & Joshua N. Beilke & Lewis L. Lanier, 2009. "Erratum: Adaptive immune features of natural killer cells," Nature, Nature, vol. 457(7233), pages 1168-1168, February.
    2. Joseph C. Sun & Joshua N. Beilke & Lewis L. Lanier, 2009. "Adaptive immune features of natural killer cells," Nature, Nature, vol. 457(7229), pages 557-561, January.
    Full references (including those not matched with items on IDEAS)

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