A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment

Publication date: 15 August 2017
Source:Immunity, Volume 47, Issue 2
Author(s): Frederic Sierro, Maximilien Evrard, Simone Rizzetto, Michelle Melino, Andrew J. Mitchell, Manuela Florido, Lynette Beattie, Shaun B. Walters, Szun Szun Tay, Bo Lu, Lauren E. Holz, Ben Roediger, Yik Chun Wong, Alessandra Warren, William Ritchie, Claire McGuffog, Wolfgang Weninger, David G. Le Couteur, Florent Ginhoux, Warwick J. Britton, William R. Heath, Bernadette M. Saunders, Geoffrey W. McCaughan, Fabio Luciani, Kelli P.A. MacDonald, Lai Guan Ng, David G. Bowen, Patrick Bertolino
The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas 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 harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.

Graphical abstract

Teaser

The hepatic sinusoids harbor a well-characterized resident macrophage population, Kupffer cells. Sierro et al. report an additional liver-resident macrophage population occupying the hepatic capsule, phenotypically and developmentally distinct from Kupffer cells, which plays a role in immunosurveillance by sensing peritoneal pathogens and recruiting neutrophils to control intrahepatic bacterial dissemination.


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