Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis.

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 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.

A historical perspective of Kupffer cells in the context of infection.

The Kupffer cell was first discovered by Karl Wilhelm von Kupffer in 1876, labeling them as "Sternzellen." Since their discovery as the primary macrophages of the liver, researchers have gradually gained an in-depth understanding of the identity, functions, and influential role of Kupffer cells, particularly in infection. It is becoming clear that Kupffer cells perform important tissue-specific functions in homeostasis and disease.

A Functional Assessment of Fetal Liver and Monocyte-Derived Macrophages in the Lung Alveolar Environment.

It is becoming clear that every organ is seeded by a population of fetal liver-derived macrophages that are replaced at different rates by monocyte-derived macrophages. Using the Ms4a3tdTomato reporter mouse that reports on monocyte-derived alveolar macrophages (Mo-AMs) and our ability to examine AM function using our multichannel intravital microscopy, we examined the fetal-liver derived alveolar macrophage (FL-AM) and Mo-AM populations within the same mouse under various environmental conditions. The experiments unveiled that AMs migrated from alveolus to alveolus and phagocytosed bacteria identically regardless of ontogenic origin.