Immune surveillance by a contiguous network of monocyte-derived macrophages residing in the hepatic capsule (#28)
The liver is strategically positioned at the interface between two routes traversed by pathogens in disseminating infection. While blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbours a contiguous cellular network of liver-resident macrophages (LCMs) phenotypically distinct from KCs. In contrast to KCs, LCMs were not embryonically derived, but replenished in the steady state from blood monocytes, and their numbers increased after weaning in a microbiota-dependent process. LCMs were able to sense peritoneal bacteria reaching the capsule and recruited neutrophils to promote their elimination. LCMs did not efficiently present or cross-present antigens to naive CD8 T cells. Specific ablation of LCMs resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by two distinct resident macrophage populations, with distinct complementary roles in immunosurveillance.