Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells.
Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells.
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DOI：
10.1038/s41467-023-42182-w
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发表时间：
2023-10-12
影响因子：
16.6
通讯作者：
Brizic, Ilija
中科院分区：
文献类型：
--
作者：
Rozmanic, Carmen;Lisnic, Berislav;Pribanic Matesic, Marina;Mihalic, Andrea;Hirsl, Lea;Park, Eugene;Lesac Brizic, Ana;Indenbirken, Daniela;Viduka, Ina;Santic, Marina;Adler, Barbara;Yokoyama, Wayne M.;Krmpotic, Astrid;Juranic Lisnic, Vanda;Jonjic, Stipan;Brizic, Ilija
与成年感染相比，早期感染可引起不同的免疫反应和发病机制。在这里，我们研究小鼠巨细胞病毒感染新生小鼠对NK细胞的影响。我们发现感染严重影响新生儿NK细胞的成熟和功能。这种影响并不是由于病毒控制受损造成的。感染引起的炎性反应使控制NK细胞命运的主要转录因子的表达失调，如Eome，导致NK细胞功能受损。最显著的是，来自围产期感染小鼠的NK细胞产生干扰素-γ的能力减弱，这是由于长非编码RNA IFNG-AS1的表达下调所致。此外，骨髓有效地产生新的NK细胞的能力降低，这解释了围产期感染对NK细胞的长期负面影响。这项研究表明，生命早期的病毒感染可以深刻地影响NK细胞生物学，包括NK细胞功能的长期损害。众所周知，早期生命感染会影响和调节晚年的免疫反应。在这里，作者表明，围产期感染小鼠巨细胞病毒导致小鼠NK细胞转录模式和功能的改变。
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. Early life infections are known to impact and modulate the immune response in later life. Here the authors show that perinatal infection with murine cytomegalovirus results in a modified transcriptional profile and functionality in murine NK cells.
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影响因子：
30.5
作者：
Cortez VS;Ulland TK;Cervantes-Barragan L;Bando JK;Robinette ML;Wang Q;White AJ;Gilfillan S;Cella M;Colonna M
通讯作者：
Colonna M
影响因子：
8
作者：
Collins, Amelie;Rothman, Nyanza;Reiner, Steven L.
通讯作者：
Reiner, Steven L.
影响因子：
3.6
作者：
BOPPANA, SB;PASS, RF;ALFORD, CA
通讯作者：
ALFORD, CA
影响因子：
8
作者：
Alvarez, Maite;Simonetta, Federico;Negrin, Robert S.
通讯作者：
Negrin, Robert S.
影响因子：
5.4
作者：
Hokeness, Kirsten L.;Deweerd, Elizabeth S.;Salazar-Mather, Thais P.
通讯作者：
Salazar-Mather, Thais P.