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

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. Yokoyama, Astrid Krmpotić, Vanda Juranić Lisnić, Stipan Jonjić, Ilija Brizić

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article number6412
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

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