Impact Factor 5.511

Among the world's top 10 most-cited Immunology journals

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.02948

The role of monocytes and macrophages in acute and acute-on-chronic liver failure

 Evangelos Triantafyllou1, 2,  Kevin J. Woollard2, Mark J. McPhail3, Charalambos G. Antoniades1 and  Lucia A. Possamai1, 2*
  • 1Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College London, United Kingdom
  • 2Division of Immunology and Inflammation, Department of Medicine, Imperial College London, United Kingdom
  • 3Division of Liver Studies, Department of Transplantation Immunology & Muscosal Biology, King's College London, United Kingdom

Acute and acute-on-chronic liver failure (ALF and ACLF), though distinct clinical entities, are considered syndromes of innate immune dysfunction. Patients with ALF and ACLF display evidence of a pro-inflammatory state with local liver inflammation, features of systemic inflammatory response syndrome (SIRS) and vascular endothelial dysfunction that drive progression to multi-organ failure. In an apparent paradox, these patients are concurrently immunosuppressed, exhibiting acquired immune defects that render them highly susceptible to infections. This paradigm of tissue injury succeeded by immunosuppression is seen in other inflammatory conditions such as sepsis, which share poor outcomes and infective complications that account for high morbidity and mortality. Monocyte and macrophage dysfunction are central to disease progression of ALF and ACLF. Activation of liver-resident macrophages (Kupffer cells) by pathogen and damage associated molecular patterns leads to the recruitment of innate effector cells to the injured liver. Early monocyte infiltration may contribute to local tissue destruction during the propagation phase and results in secretion of pro-inflammatory cytokines that drive SIRS. In the hepatic microenvironment, recruited monocytes mature into macrophages following local reprogramming so as to promote resolution responses in a drive to maintain tissue integrity. Intra-hepatic events may affect circulating monocytes through spill over of soluble mediators and exposure to apoptotic cell debris during passage through the liver. Hence, peripheral monocytes show numerous acquired defects in acute liver failure syndromes that impair their anti-microbial programmes and contribute to enhanced susceptibility to sepsis. This review will highlight the cellular and molecular mechanisms by which monocytes and macrophages contribute to the pathophysiology of ALF and ACLF, considering both hepatic inflammation and systemic immunosuppression. We identify areas for further research and potential targets for immune-based therapies to treat these devastating conditions.

Keywords: Acute liver failure (ALF), Acute-on chronic liver failure, Monocytes, Macrophages, Immunosuppression, liver inflammation, DAMPs (damage-associated molecular patterns), PAMPs (Pathogen-associated molecular patterns)

Received: 29 Sep 2018; Accepted: 30 Nov 2018.

Edited by:

Hannelie Korf, Faculty of Medicine, KU Leuven, Belgium

Reviewed by:

Jonel Trebicka, Universität Bonn, Germany
Maria R. D'Império Lima, University of São Paulo, Brazil  

Copyright: © 2018 Triantafyllou, Woollard, McPhail, Antoniades and Possamai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Lucia A. Possamai, Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College London, London, United Kingdom, l.possamai@imperial.ac.uk