Monocyte-derived Galectin-9 and PD-L1 differentially impair adaptive and innate immune response in chronic HBV infection and their expression remain unaltered after antiviral therapy.

Introduction: Patients with chronic HBV infection (CHI) exhibit defective anti-viral immune-response whose underlying causes still remain unclear. Monocytes act as immune sentinels for pathogens and can regulate immunity via interaction with other immune-cells, apart from differentiating into macrophages. Immune-checkpoint molecules (ICMs) expressed by immune-cells, including monocytes are known to negatively regulate immune-responses.

Hemin-induced reactive oxygen species triggers autophagy-dependent macrophage differentiation and pro-inflammatory responses in THP-1 cells.

The toxic effect of oxidized-heme, also known as hemin, is implicated in developing adverse clinical outcome in various hematolytic diseases. To simulate and reconstruct the molecular events associated with hemin exposure on circulating monocytes, we employed a THP-1 cell line based in vitro model. Flow cytometry and Western blot analyses were subsequently applied.

Multifaceted Defects in Monocytes in Different Phases of Chronic Hepatitis B Virus Infection: Lack of Restoration after Antiviral Therapy.

Monocytes play an important role in the control of microbial infection, but monocyte biology during chronic hepatitis B virus (HBV) infection (CHI) remains inadequately studied. We investigated the frequency, phenotype, and functions of monocyte subsets in different phases of CHI, namely, immune tolerance (IT), hepatitis B early antigen (HBeAg)-positive/HBeAg-negative chronic hepatitis B (EP-/EN-CHB, respectively), and inactive carrier (IC), identified factors responsible for their functional alterations, and determined the impact of antiviral therapy on these cells. Flow cytometric analysis indicated that HLA-DR CD14 CD16 classical monocytes were significantly reduced while HLA-DR CD14 CD16 intermediate and HLA-DR CD14 CD16 nonclassical monocytes were expanded in IT and EP-/EN-CHB compared with those in IC and healthy controls (HC).

Diverse facets of MDSC in different phases of chronic HBV infection: Impact on HBV-specific T-cell response and homing.

Background And Aims: Chronic HBV infection (CHI) is associated with a diverse natural history that includes immune-tolerant (IT), HBeAg-positive chronic hepatitis B (CHB) (EP-CHB), inactive carrier, and HBeAg-negative CHB (EN-CHB) phases. A hallmark of CHI is impairment of HBV-specific T-cell response. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as key regulator of T cells, and their properties are sculpted by their microenvironment.

CD8CD28 T cells: key cytotoxic players impacting disease pathogenesis in chronic HBV infection.

During chronic hepatitis B (CHB), CD8 T cells down-regulate CD28, the primary co-stimulation molecule for T-cell activation. Diverse functional attributes of CD8CD28 T cells are suggested in various disease contexts. The present study aimed to characterize CD8CD28 T cells in different phases of chronic Hepatitis B virus (HBV) infection (CHI)- Immune-tolerance (IT), Hepatitis B e-antigen-positive CHB (EP-CHB), Inactive carriers (IC) and Hepatitis B e-antigen-negative CHB (EN-CHB), to appraise their contribution in HBV-related disease pathophysiology.

Myeloid-derived suppressor cells induce regulatory T cells in chronically HBV infected patients with high levels of hepatitis B surface antigen and persist after antiviral therapy.

Background: CD4 regulatory T-cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity, although the underlying mechanism remains largely elusive. Myeloid-derived suppressor cells (MDSC) have been linked with T-cell dysfunction but questions remain regarding their persistence/profile/function in chronically HBV infected patients.

Aim: To characterise MDSC in different phases of chronic HBV infection namely, immune-tolerant (IT), hepatitis B e-antigen-positive chronic hepatitis B (EP-CHB), inactive carriers (IC) and hepatitis B e-antigen-negative chronic hepatitis B (EN-CHB), to investigate their role in Treg induction and evaluate the effect of anti-viral therapy on these cells.