Immune surveillance by a contiguous network of monocyte-derived macrophages residing in the hepatic capsule — ASN Events

Immune surveillance by a contiguous network of monocyte-derived macrophages residing in the hepatic capsule (#28)

Frederic Sierro 1 2 3 , Maximilien Evrard 4 , Simone Rizzetto 5 , Michelle Melino 6 , Andrew J. Mitchell 7 , Manuela Florido 2 , Lynette Beattie 6 8 , Shaun B Walters 2 , Szun S Tay 2 , Bo Lu 2 9 , Lauren E. Holz 7 , Ben Roediger 2 , Yik C Wong 2 , Alessandra Warren 10 , William Ritchie 2 , Claire McGuffog 2 , Wolfgang Weninger 2 , David G. Le Couteur 10 , Florent Ginhoux 4 , Warwick Britton 2 , William R. Heath 8 , Geoffrey W. McCaughan 2 , Bernadette M . Saunders 2 , Fabio Luciani 5 , Kelli P. MacDonald 6 , Lai G Ng 4 , David G. Bowen 2 , Patrick Bertolino 2
  1. Australian Nuclear Science and Technology Association, Kirrawee DC, NSW, Australia
  2. Centenary Institute , Sydney
  3. University of Sydney, Sydney
  4. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR),, Singapore
  5. Inflammation and Infection Research Centre, School of Medical Sciences, UNSW, Sydney
  6. Antigen Presentation and Immunoregulation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane
  7. Department of Chemical & Biomolecular Engineering, University of Melbourne, Melbourne
  8. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne
  9. Immunology Research Centre,, St. Vincent’s Hospital, Melbourne
  10. CERA and ANZAC Research Institute, Concord RG Hospital, Sydney

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.

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