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Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells
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 functi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570381/ https://www.ncbi.nlm.nih.gov/pubmed/37828009 http://dx.doi.org/10.1038/s41467-023-42182-w |
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author | Rožmanić, Carmen Lisnić, Berislav Pribanić Matešić, Marina Mihalić, Andrea Hiršl, Lea Park, Eugene Lesac Brizić, Ana Indenbirken, Daniela Viduka, Ina Šantić, Marina Adler, Barbara Yokoyama, Wayne M. Krmpotić, Astrid Juranić Lisnić, Vanda Jonjić, Stipan Brizić, Ilija |
author_facet | Rožmanić, Carmen Lisnić, Berislav Pribanić Matešić, Marina Mihalić, Andrea Hiršl, Lea Park, Eugene Lesac Brizić, Ana Indenbirken, Daniela Viduka, Ina Šantić, Marina Adler, Barbara Yokoyama, Wayne M. Krmpotić, Astrid Juranić Lisnić, Vanda Jonjić, Stipan Brizić, Ilija |
author_sort | Rožmanić, Carmen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10570381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105703812023-10-14 Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells Rožmanić, Carmen Lisnić, Berislav Pribanić Matešić, Marina Mihalić, Andrea Hiršl, Lea Park, Eugene Lesac Brizić, Ana Indenbirken, Daniela Viduka, Ina Šantić, Marina Adler, Barbara Yokoyama, Wayne M. Krmpotić, Astrid Juranić Lisnić, Vanda Jonjić, Stipan Brizić, Ilija Nat Commun Article 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. Nature Publishing Group UK 2023-10-12 /pmc/articles/PMC10570381/ /pubmed/37828009 http://dx.doi.org/10.1038/s41467-023-42182-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rožmanić, Carmen Lisnić, Berislav Pribanić Matešić, Marina Mihalić, Andrea Hiršl, Lea Park, Eugene Lesac Brizić, Ana Indenbirken, Daniela Viduka, Ina Šantić, Marina Adler, Barbara Yokoyama, Wayne M. Krmpotić, Astrid Juranić Lisnić, Vanda Jonjić, Stipan Brizić, Ilija Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title | Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title_full | Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title_fullStr | Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title_full_unstemmed | Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title_short | Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells |
title_sort | perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of nk cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570381/ https://www.ncbi.nlm.nih.gov/pubmed/37828009 http://dx.doi.org/10.1038/s41467-023-42182-w |
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