Early life myeloid immune cells in the neonatal liver

The translocation of macromolecules across the mammalian intestinal epithelial barrier is enhanced in early life before ceasing at what has been termed gut closure. However, the translocated macromolecules, the mechanism of translocation, and the functional consequences for the neonatal liver, which is still a hematopoietic organ at this age in mice, have not been defined. Microbiota profiling identified a transiently increased abundance of small intestinal lipopolysaccharide (LPS)-producing g-Proteobacteria early after birth. Orally administered LPS was translocated across the mucosal barrier during this early postnatal window, resulting in increased hepatic cytokine expression. LPS translocation was independent of disabled homolog 2 (Dab2)-mediated endocytosis by fetal-like enterocytes, but was mediated by the fatty acid translocase CD36, which showed transient overexpression early after birth. Postnatal LPS exposure altered hepatic haematopoiesis, innate immune reactivity and the bacterial clearance capacity of the neonatal liver. Taken together, our results identify and characterise a postnatal time window of hepatic tissue stimulation by gut-derived LPS as a novel immune priming event in early life. To investigate the effect of gut-derived LPS on neonatal hepatic immune cells, mice were daily treated with oral LPS (2.5 µg/g BW) from P1 to P4 every 24h (N=3). 2h after the last LPS treatment on P4, mice were analysed by single-cell RNA sequencing of hepatic immune cells.