TY - JOUR
T1 - Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells
AU - Rožmanić, Carmen
AU - Lisnić, Berislav
AU - Pribanić Matešić, Marina
AU - Mihalić, Andrea
AU - Hiršl, Lea
AU - Park, Eugene
AU - Lesac Brizić, Ana
AU - Indenbirken, Daniela
AU - Viduka, Ina
AU - Šantić, Marina
AU - Adler, Barbara
AU - Yokoyama, Wayne M.
AU - Krmpotić, Astrid
AU - Juranić Lisnić, Vanda
AU - Jonjić, Stipan
AU - Brizić, Ilija
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85174198576&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-42182-w
DO - 10.1038/s41467-023-42182-w
M3 - Article
C2 - 37828009
AN - SCOPUS:85174198576
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6412
ER -