High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus

Jacobus Herderschee; Tytti Heinonen; Craig Fenwick; Irene T Schrijver; Khalid Ohmiti; Darius Moradpour; Matthias Cavassini; Giuseppe Pantaleo; Thierry Roger; Thierry Calandra; Swiss HIV Cohort Study

doi:10.1016/j.cmi.2021.08.018

High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus

Clin Microbiol Infect. 2022 Apr;28(4):611.e1-611.e7. doi: 10.1016/j.cmi.2021.08.018. Epub 2021 Aug 30.

Collaborators

Swiss HIV Cohort Study:
K Aebi-Popp, A Anagnostopoulos, M Battegay, E Bernasconi, J Böni, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, C R Kahlert, L Kaiser, O Keiser, T Klimkait, R D Kouyos, H Kovari, B Ledergerber, G Martinetti, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, D Nicca, P Paioni, G Pantaleo, M Perreau, A Rauch, C Rudin, A U Scherrer, P Schmid, R Speck, M Stöckle, P Tarr, A Trkola, P Vernazza, G Wandeler, R Weber, S Yerly

Affiliations

¹ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
² Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Division of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Swiss Vaccine Research Institute, Lausanne, Switzerland.
⁵ Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address: Thierry.Calandra@chuv.ch.

PMID: 34474121
DOI: 10.1016/j.cmi.2021.08.018

Abstract

Objectives: Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy.

Methods: Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection.

Results: HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56^dim natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) 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.

Conclusions: Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.

Keywords: Adaptive immunity; Direct-acting antiviral therapy; Hepatitis C virus; Human immunodeficiency virus; Innate immunity; Mass cytometry; Single cell.

MeSH terms

Antiviral Agents / therapeutic use
CD8-Positive T-Lymphocytes
HIV Infections* / complications
HIV Infections* / drug therapy
Hepacivirus
Hepatitis C* / complications
Hepatitis C* / drug therapy
Hepatitis C, Chronic* / drug therapy
Humans

Substances

Antiviral Agents