Hepatitis B Core Antigen Impairs the Polarization While Promoting the Production of Inflammatory Cytokines of M2 Macrophages via the TLR2 Pathway

Abstract

Although several evidences suggesting the vital roles that innate immunity plays in the persistence and elimination of chronic hepatitis B virus (CHB) infection, the exact mechanism is still complicated. Here, we successfully polarized monocytes derived from healthy human peripheral blood mononuclear cells (PBMCs) into M1/M2 macrophages and detected the effects of hepatitis B core antigen (HBcAg) on the polarization and function of macrophages via the Toll-like receptor (TLR) 2 signaling pathway. The results showed that HBcAg had a negligible impact on M1 polarization, while it effectively impaired M2 polarization and promoted the production of pro-inflammatory cytokines such as IL-6 and TNF-α. Additionally, HBcAg treatment increased TLR2 expression on M2 macrophages and TLR2 blockade abolished the effects of HBcAg on the impaired phenotype and pro-inflammatory cytokine productions of M2 macrophages. Signaling pathway analysis revealed that the nuclear factor κB (NF-κB) pathway, the downstream of TLR2, was upregulated upon HBcAg treatment in both M1 and M2 macrophages. Furthermore, a CD8 + T-macrophage coculture system implied that compared with PBS stimulation, HBcAg-stimulated M2 macrophages regained their ability to activate CD8 + T cells with higher secretion of IFN-γ. Finally, we found impaired expression of M2-related molecules and increased levels of pro-inflammation cytokines in M2 macrophages from CHB patients upon HBcAg stimulation. In conclusion, these results imply a favorable role of HBcAg in the establishment of a pro-inflammatory microenvironment by macrophages, which may suggest a potential therapeutic strategy of HBcAg-induced macrophage activation in CHB infection.

Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

“…It is an important gene in the immune in ammatory mechanism of DN [ 35 ]. It is closely related to mesangial matrix proliferation, basement membrane thickening, podocyte damage, and renal tubular epithelial cell transdifferentiation [ 36 ]; IL6 and TNF have immunomodulatory and proin ammatory effects [ 37 ]; VEGFA is related to the vascular permeability of patients with DN [ 38 ]; the activation of EGFR upregulates the production of ROS and endoplasmic reticulum stress, and the onset of DN plays an important role in this mechanism [ 39 ]. Therefore, it can be inferred that luteolin, tanshinone IIA, and salvianolic acid B, the main components of salvianolic acid B, can reduce oxidative stress and inhibit the expression of in ammatory mediators such as IL-10, IL-6, TNF, etc., thus delaying DN progression.…”

“…In addition, other studies have shown that the interaction between AGEs and RAGE leads to vasoconstriction, procoagulant state [ 48 ], accelerates renal vascular aging and injury [ 49 ], and further promotes DN progression. (2) Immune in ammation regulation: TNF has immunomodulatory and proin ammatory effects [37]. TNF-α stimulates the aggregation and adhesion of in ammatory cells, increases the permeability of microvessels, and impairs glomeruli through an in ammatory response [ 50 ].…”

The Differentiation of Human Cytomegalovirus Infected-Monocytes Is Required for Viral Replication

“…For example, Asian-lineage Zika virus (ZIKV) polarizes infected monocytes toward M2 macrophages that express anti-inflammatory cytokines such as IL-10 that likely suppress the adaptive immune response in pregnant women (Foo et al, 2017 ). In addition, hepatitis B core antigen triggers M2 polarization of monocytes via TLR2-singaling pathway (Yi et al, 2020 ). In line with these observations, we have documented that HCMV polarizes monocyte differentiation into inflammatory macrophages (Chan et al, 2009a ; Stevenson et al, 2014 ) with a specific bias toward an M1 phenotype.…”

Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking

“…It is closely related to mesangial matrix proliferation, basement membrane thickening, podocyte damage, and renal tubular epithelial cell transdifferentiation [ 36 ]. IL6 and TNF have immunomodulatory and pro-inflammatory effects [ 37 ]. VEGFA is related to vascular permeability in patients with DN [ 38 ].…”