Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-alpha in patients with chronic hepatitis B.

Abstract

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by hepatitis B virus (HBV) infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis and liver cancer. Interferon-alpha (IFN-alpha) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-alpha on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-alpha therapy. Notably, we identified three CHB-specific cell subsets, Pro-infla CD14 + monocytes, Pro-infla CD16 + monocytes and IFN + CX3CR1- NK cells, which highly expressed pro-inflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-alpha treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-alpha treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-alpha-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-alpha, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.