Immune and metabolic shifts during neonatal development reprogram liver identity and function

Journal of Hepatology
Brenda Naemi NakagakiGustavo B Menezes

Abstract

The liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, how the liver adapts both the immune system and enzymatic profile to challenges in the postnatal period remains elusive. We aimed to identify the mechanisms underlying this adaptation. We analyzed liver samples from mice on day 0 after birth until adulthood. Human biopsies from newborns and adults were also examined. Liver immune cells were phenotyped using mass cytometry (CyTOF) and expression of several genes belonging to immune and metabolic pathways were measured. Mortality rate, bacteremia and hepatic bacterial retention after E. coli challenge were analyzed using intravital and in vitro approaches. In a set of experiments, mice were prematurely weaned and the impact on gene expression of metabolic pathways was evaluated. Human and mouse newborns have a sharply different hepatic cellular composition and arrangement compared to adults. We also found that myeloid cells and immature B cells primarily compose the neonatal hepatic immune system. Although neonatal mice were more susceptible to infections, a rapid evolution to an efficient immune response was observed. Concomitantly, newborns displayed...Continue Reading

Citations

Apr 13, 2019·Immunological Reviews·Bruna A David, Paul Kubes
May 21, 2019·Journal of Leukocyte Biology·Kassiana MafraGustavo Batista Menezes
Jun 4, 2020·Journal of Developmental Origins of Health and Disease·Luana Lopes SouzaPatricia Cristina Lisboa
Sep 26, 2020·Frontiers in Immunology·Miguel A ZarateClyde J Wright
Dec 16, 2020·The Journal of Clinical Investigation·Evangelos TriantafyllouMark R Thursz
Jul 5, 2019·Brain, Behavior, and Immunity·Roberta Cristelli FonsecaAndré Gustavo Oliveira
Sep 9, 2021·Journal of Virology·Ana Cláudia Dos Santos Pereira AndradeVivian Vasconcelos Costa

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