Kupffer cell-like syncytia replenish resident macrophage function in fibrotic liver

Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods
to parenchymal cells to maintain their identity and serve as the body’s
central bacterial filter. Liver cirrhosis dramatically alters vascular
architecture, but how KCs adapt is unclear. We used a mouse model of liver
fibrosis and human tissue to examine immune adaptation. Fibrosis forced
KCs to lose contact with parenchymal cells, downregulating “KC identity”,
which rendered them incapable of clearing bacteria. Commensals stimulated
the recruitment of monocytes via CD44 to a spatially distinct vascular
compartment. There, they formed large aggregates of multinucleated cells
(syncytia) that expressed phenotypical KC markers and displayed enhanced
bacterial catching ability. Syncytia formed via CD36 and were observed in
human cirrhosis as a possible antimicrobial defense that evolved with
fibrosis.