Monocyte dysregulation: consequences for hepatic infections

Abstract

Liver disorders due to infections are a substantial health concern in underdeveloped and industrialized countries. This includes not only hepatotropic viruses (e.g., hepatitis B, hepatitis C) but also bacterial and parasitic infections such as amebiasis, leishmaniasis, schistosomiasis, or echinococcosis. Recent studies of the immune mechanisms underlying liver disease show that monocytes play an essential role in determining patient outcomes. Monocytes are derived from the mononuclear phagocyte lineage in the bone marrow and are present in nearly all tissues of the body; these cells function as part of the early innate immune response that reacts to challenge by external pathogens. Due to their special ability to develop into tissue macrophages and dendritic cells and to change from an inflammatory to an anti-inflammatory phenotype, monocytes play a pivotal role in infectious and non-infectious liver diseases: they can maintain inflammation and support resolution of inflammation. Therefore, tight regulation of monocyte recruitment and termination of monocyte-driven immune responses in the liver is prerequisite to appropriate healing of organ damage. In this review, we discuss monocyte-dependent immune mechanisms underlying hepatic infectious disorders. Better understanding of these immune mechanisms may lead to development of new interventions to treat acute liver disease and prevent progression to organ failure.

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

“…(2) monocytes (MCs) providing TNF-α, the interleukins IL-1β, IL-6, and IL-8, the chemokines CCL1, CCL2, CCL3, and CCL5, as well as growth factors such as granulocyte colony-stimulating factor (GCSF) and macrophage colony-stimulating factor(MCSF) [27];(3) hepatic stellate cells (HSCs)producing cytokines and growth factors capable of stimulating various hepatic cell types including TGFα, TGFβ, epidermal growth factor (EGF), hepatocyte growth factor (HGF), plateletderived growth factor (PDGF), stem cell factor, acidic and basic fibroblast growth factor (FGF), macrophage colony-stimulating factor, and platelet activating factor [28,29];(4) hepatic dendritic cells (HDCs)generating proinflammatory cytokines like IL-2, IL-6, IL-12,TNF-α, and INF-γ [30,31];(5) hepatic B cells (BCs)releasing the proinflammatory cytokines interferon (INF)-γ and TNFα [32];(6) hepatic T cells (TCs) secreting TNF-α, TGFβ, IL-10, and IFN-γ [33,34]; and (7) liver sinusoidal endothelial cells (LSECs) releasing chemokines and cytokines including IFN-γ [35,36].…”

Mediators of liver inflammation and carcinogenesis

“…Monocytes are a major cell type involved in liver inflammation and the response to liver infection. The review by Sellau et al in this issue [5] discusses the extraordinary This article is a contribution to the Special issue on: Mediators of liver inflammation and carcinogenesis -Guest Editors: Johannes Herkel & Dirk Schmidt-Arras plasticity of this cell population upon recruitment to the liver in the context of liver infections. The authors argue that the plastic response of monocyte-derived cells to infection can result in pathogen clearance, but sometimes also in excessive fibrosis or immunopathology.…”

Single‐cell RNA sequencing reveals transcriptional profiles of monocytes in HBV‐infected pregnant women during mid‐pregnancy

“…After HBV infection, activated monocytes produce and secrete a large number of inflammatory cytokines and chemokines to recruit inflammatory cells and clear target cells in an active and synergistic manner. Antigens are presented to T cells by MHC II molecules, resulting in the activation and proliferation of T cells, triggering an antiviral response 6,8 . During chronic HBV infection, cytokines play a critical role in immune regulation and inflammation.…”

“…Antigens are presented to T cells by MHC II molecules, resulting in the activation and proliferation of T cells, triggering an antiviral response. 6 , 8 During chronic HBV infection, cytokines play a critical role in immune regulation and inflammation. They inhibit viral replication and influence the persistence of HBV infection.…”