Kupffer cell in the immune activation and tolerance toward HBV/HCV infection

Abstract

Kupffer cells (KCs) are macrophages that are found in the sinusoids of the liver. KCs are a crucial part of the innate immune system, acting as scavengers and phagocytes. KCs and sinusoidal endothelial cells together form the first immune barrier of the portal system. Studies show that KCs can not only maintain homeostasis in the immune response, but also facilitate the pathogenesis of type B and type C hepatitis (HBV/HCV) through their antigen-presenting function and secretion of soluble mediators. KCs can express toll-like receptors (TLRs), Fas ligand (FasL) and programmed cell death ligand 1 (PD-L1), and secrete large amounts of inflammatory factors leading to immune tolerance toward HBV/HCV. On the one hand, KCs contribute to the clearance of HBV/HCV due to their nature as innate immune cells. At the same time, KCs induce immune tolerance toward HBV/HCV, which leads to chronicity of the infection. The dual role of KCs in the immune response toward HBV/HCV means it is a gigantic challenge for scientists to illuminate the detailed mechanisms involved, but it also offers important potential therapeutic targets.

Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation

“…They maintain hepatic homeostasis during immune responses to liver injury and also function as central mediators of hepatic inflammation induced in response to microbial-derived products [14–16]. The inflammatory cascade within the liver is initiated and propagated by KCs upon recognition of danger-associated molecular patterns (DAMPs) such as HMGB1 and pathogen-associated molecular patterns (PAMPs) such as viral RNA and/or viral proteins [17, 18]. Activated KCs produce and secrete a diverse array of chemokines and cytokines leading to leukocyte recruitment to the liver.…”

Microbiota-Meditated Immunity Abnormalities Facilitate Hepatitis B Virus Co-Infection in People Living With HIV: A Review

“…Polo et al, observed that hepatic damage induced by efavirenz involved acute interference with mitochondria, and similar observations have been made by other investigators (67,(71)(72)(73). The hepatic dysfunction associated with HIV infection and ART is likely to further accelerate the progression of HBV infection (63,74). It has been reported that hepatocytic mitochondrial dysfunction stimulates HBV gene expression through lipogenic transcription factor activation (74).…”

“…As the largest population of resident macrophages in the liver, Kupffer cells play a key role in liver injury, hepatic inflammation, and clearance of HBV from the liver. The protective effects of Kupffer cells are due to their inherent role as innate immune cells (59)(60)(61)(62)(63). However, as these cells also express CD4+, CCR5, and CXCR4, they are vulnerable and can be productively infected by HIV, resulting in a dysregulated hepatic innate immune response, subsequent hepatic inflammation, and fibrosis (56,64,65).…”

CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans

“…The liver has been traditionally described as a tolerogenic organ, with Kupffer cells (KCs) and dendritic cells representing the main cell subsets mediating tolerance. KCs suppress CD8 + T cell activity by several mechanisms, including overexpression of Fas-Ligand, which induces CD8 + T cell destruction (47); overexpression of PD-L1, which leads to cell exhaustion through PD-1 receptor on T cells (48); or secretion of IL-10, an immunosuppressive cytokine (49, 50). Although intrahepatic KCs have been shown in mice and rats to express TLRs (51, 52), those cells are hypo-responsive to endogenous LPS and also other TLR ligands (53).…”