High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with HCV. Clinical Microbiology and Infection
Herderschee et al. aimed to assess whether elimination of hepatitis C (HCV) with direct-acting antivirals (DAA) leads to a restoration of the immune system affected by HCV.
To answer this research question, the authors analyzed before and 12 weeks after sustained virological response (SVR12) to DAA therapy 22 cell populations by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with or without human immunodeficiency virus (HIV) infection.
They found that HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies of intermediate monocytes, non-classical monocytes, conventional dendritic cells type 2 and CD56dim natural killer cells were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells activated CD4 T cells and activated CD8 T cells were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12.
In conclusion, high-dimensional immune profiling of blood cells provided a broad and in-depth picture of the systemic immune dysregulation induced by chronic HCV. A salient finding was the observation of a profound derangement of the homeostasis of the immune system triggered by HCV, characterized by a pro-inflammatory innate immune signature extending well beyond the clearance of HCV, especially in HCV/HIV-infected patients. This inflammatory phenotype may contribute to the pathogenesis of systemic complications of chronic HCV infection.