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.
Highlights
Chronic hepatitis B virus (HBV) infection is one of the most serious public health problems, with approximately 400 million HBV carriers worldwide, and 1–2 million people succumbing to HBV-induced liver cirrhosis and hepatocellular carcinoma each year, especially in China where approximately 22 million people suffer from chronic hepatitis B (CHB) [1]
These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in chronic hepatitis B virus (CHB) patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease
P values are shown. (B) The absolute numbers of peripheral blood monocytes was significantly correlated with serum ALT levels but not with HBV
Summary
Chronic hepatitis B virus (HBV) infection is one of the most serious public health problems, with approximately 400 million HBV carriers worldwide, and 1–2 million people succumbing to HBV-induced liver cirrhosis and hepatocellular carcinoma each year, especially in China where approximately 22 million people suffer from chronic hepatitis B (CHB) [1]. Recent studies have shown that nonspecific lymphocytes are significantly infiltrated in livers of CHB patients, such as dendritic cells (DCs), natural killer cells, Th17 cells and Treg cells, playing distinct roles in modulating the inflammatory process [4,5,6,7]. These findings, suggest that multiple types of immune cells may actively participate in HBVassociated liver pathogenesis [8]. Understanding the reciprocal linkage between immune cells during chronic HBV infection is a prerequisite for developing effective treatment strategies for the disease. Little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages
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