Hyper-Activated Pro-Inflammatory CD16+ Monocytes Correlate with the Severity of Liver Injury and Fibrosis in Patients with Chronic Hepatitis B

Abstract

BackgroundExtensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages.Methodology/Principal FindingsThe frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16+ subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16− monocytes/macrophages. Furthermore, peripheral blood CD16+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores.ConclusionsThese distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

“…Many different cell types, including T lymphocytes, monocytes and DCs, are primed in ACLF, and these are believed to play a pivotal role in the pathogenesis of this disease. [6][7][8][9][10][11] Corticosteroids have been used for the treatment of severe acute hepatic failure by either oral or intravenous administration. Mechanically, corticosteroids can suppress the effects of activated macrophages, DC subsets and other inflammatory cells, [10][11] which indicates that there is a reciprocal effect on the efficacy of therapy.…”

“…[6][7][8][9][10][11] These changes include exacerbated innate immunologic responses, such as the activation of monocytes/macrophages and lymphocytes and cytokine release from these inflammatory cells. Clinical findings and experimental rodent models suggest that corticosteroids can suppress the effects of these activated inflammatory cells.…”

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

“…For intracellular staining, these cells were incubated in RPMI 1640 medium supplemented with 10% FCS for 6 h as previously described (26). Monensin (0.4 mM, BD Pharmingen) was added during the first hour of incubation.…”

Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

“…During inflammatory conditions, such as sepsis [6,7] , bacterial [8] or viral [9][10][11] infections and a wide range of inflammatory diseases (reviewed by [1] ), the frequency of IM or both IM and NCM is increased. However, as patients with inflammation cannot be identified before displaying clinical symptoms, little is known about the monocyte subsets during the earliest stages of inflammation.…”