1. Toll-like Receptor Expression and Signaling in Peripheral Blood Mononuclear Cells Correlate With Clinical Outcomes in Acute Hepatitis C Virus Infection.
- Author
-
Chen Yi Mei SL, Burchell J, Skinner N, Millen R, Matthews G, Hellard M, Dore GJ, Desmond PV, Sundararajan V, Thompson AJ, Visvanathan K, and Sasadeusz J
- Subjects
- Adult, Australia, B7-2 Antigen analysis, Cytokines metabolism, Female, Humans, Leukocytes, Mononuclear chemistry, Longitudinal Studies, Male, Middle Aged, Treatment Outcome, Hepatitis C immunology, Leukocytes, Mononuclear immunology, Signal Transduction, Toll-Like Receptor 2 analysis, Toll-Like Receptor 4 analysis
- Abstract
Background: Mechanisms by which spontaneous clearance of acute hepatitis C occurs are unclear. A critical role for the innate immune system and IFNL4 polymorphisms has been proposed. This study investigates whether Toll-like receptor (TLR) expression and signaling during acute hepatitis C correlates with clinical outcomes., Methods: Participants identified from the Australian Trial in Acute Hepatitis C and the Networks study were followed longitudinally from the time of diagnosis of acute hepatitis C. Peripheral blood mononuclear cells (PBMCs) and plasma were collected at and 2 time points after diagnosis. At each time point, TLR2, TLR4, and CD86 expression on peripheral blood monocytes, natural killer (NK) cells, and NK T cells was measured, as well as the response of PBMCs to stimulation with TLR ligands. Cytokine and chemokine levels were measured in stimulated PBMCs and plasma., Results: We identified 20 participants with acute hepatitis C (10 with hepatitis C virus [HCV] monoinfection and 10 with HCV and human immunodeficiency virus coinfection). Eleven participants (55%) spontaneously cleared HCV. Acute hepatitis C and spontaneous clearance was associated with lower TLR4 expression on monocytes (P = .009) and NK cells (P = .029). Acute hepatitis C and spontaneous clearance was also associated with a reduced interferon γ response to TLR4 (P = .038) and TLR7/8 stimulation (P = .035), a reduced interleukin 6 response to TLR7/8 stimulation (P = .037), and reduced IFN-γ-inducible protein 10 (IP-10) response to TLR2 stimulation (P = .042). Lower plasma IP-10 levels were associated with spontaneous clearance (P = .001)., Conclusions: These findings implicate TLR4 signaling as playing a critical role in the outcome of acute hepatitis C., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Published
- 2016
- Full Text
- View/download PDF