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Updated: Jun 8, 2025
Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis
Bruna Araujo David1,2, Jawairia Atif3,4, Fernanda Vargas E Silva Castanheira1,2
1Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Abstract:
In adults, liver-resident macrophages, or Kupffer cells (KCs), reside in the sinusoids and sterilize circulating blood by capturing rapidly flowing microbes. We developed quantitative intravital imaging of 1-day-old mice combined with transcriptomics, genetic manipulation, and in vivo infection assays to interrogate increased susceptibility of newborns to bloodstream infections. Whereas 1-day-old KCs were better at catching Escherichia coli in vitro, we uncovered a critical 1-week window postpartum when KCs have limited access to blood and must translocate from liver parenchyma into the sinusoids. KC migration was independent of the microbiome but depended on macrophage migration inhibitory factor, its receptor CD74, and the adhesion molecule CD44. On the basis of our findings, we propose a model of progenitor macrophage seeding of the liver sinusoids via a reverse transmigration process from liver parenchyma. These results also illustrate the importance of developing newborn mouse models to understand newborn immunity and disease.
Insights
Newborns are susceptible to infections because liver Kupffer cells (KCs) migrate from liver tissue into blood vessels during the first week postpartum. This migration impacts their ability to clear microbes, affecting newborn immunity.
Area of Science:
- Immunology
- Developmental Biology
- Microbiology
Background:
- Liver-resident macrophages, Kupffer cells (KCs), are crucial for sterilizing blood in adults.
- Newborns exhibit increased susceptibility to bloodstream infections, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms behind increased susceptibility to bloodstream infections in newborns.
- To understand the development and function of Kupffer cells in early life.
Main Methods:
- Quantitative intravital imaging in 1-day-old mice.
- Transcriptomics and genetic manipulation.
- In vivo infection assays with *Escherichia coli*.
Main Results:
- Despite being efficient at capturing *E. coli* in vitro, KCs in 1-week-old mice exhibit limited access to blood.
- KCs translocate from liver parenchyma into sinusoids during a critical postpartum window.
- KC migration depends on macrophage migration inhibitory factor, CD74, and CD44, and is independent of the microbiome.
Conclusions:
- A novel model of progenitor macrophage seeding of liver sinusoids via reverse transmigration is proposed.
- Understanding KC development and migration is vital for addressing newborn immunity and disease.
- Newborn mouse models are essential for studying neonatal immunity.
