Ontogeny, functions and reprogramming of Kupffer cells upon infectious disease

Abstract

The liver is a vital metabolic organ that also performs important immune-regulatory functions. In the context of infections, the liver represents a target site for various pathogens, while also having an outstanding capacity to filter the blood from pathogens and to contain infections. Pathogen scavenging by the liver is primarily performed by its large and heterogeneous macrophage population. The major liver-resident macrophage population is located within the hepatic microcirculation and is known as Kupffer cells (KCs). Although other minor macrophages reside in the liver as well, KCs remain the best characterized and are the best well-known hepatic macrophage population to be functionally involved in the clearance of infections. The response of KCs to pathogenic insults often governs the overall severity and outcome of infections on the host. Moreover, infections also impart long-lasting, and rarely studied changes to the KC pool. In this review, we discuss current knowledge on the biology and the various roles of liver macrophages during infections. In addition, we reflect on the potential of infection history to imprint long-lasting effects on macrophages, in particular liver macrophages.

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

“…This heterogeneity mirrors the intricate and dynamic immune environment, allowing liver macrophages to adapt and efficiently respond to a wide range of physiological and pathological conditions within the organ16. According to current research, the normal liver comprises at least three cellular groups composed of the mononuclear-macrophage lineage (1): Resident macrophages: KCs (2); Infiltrating macrophages: including monocyte-derived macrophages(MoMFs), peritoneal macrophages, and splenic macrophages(SMs) (3); Specialized macrophages: such as central vein macrophages(CVMs), pericentral macrophages, liver capsule macrophages(LCMs), liver sinusoidal endothelial cell (LSEC)-associated macrophages(LSEC-AMs), hepatic stellate cell(HSC)-associated macrophages(HSC-AMs) ( 12 – 14 ). The liver macrophage population is highly dynamic.…”

Liver macrophages revisited: The expanding universe of versatile responses in a spatiotemporal context

“…Their cytoplasmic expansions reach out through the sinusoids, enabling them to establish direct membrane contacts with hepatocytes. During homeostasis, KCs are predominantly favoring the liver immune tolerance (reviewed in the work by Musrati et al 3,4). Despite the KC predominance within the parenchyma, it is increasingly recognized that the liver contains at least two additional macrophage populations during homeostasis: bile duct–associated and subcapsular macrophages with distinct ontogeny and functions 5,6 .…”