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Toll-like Receptor Expression and Signaling in Peripheral Blood Mononuclear Cells Correlate With Clinical Outcomes in Acute Hepatitis C Virus Infection.
- Source :
- Journal of Infectious Diseases; 9/1/2016, Vol. 214 Issue 5, p739-747, 9p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>These findings implicate TLR4 signaling as playing a critical role in the outcome of acute hepatitis C. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221899
- Volume :
- 214
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 117384376
- Full Text :
- https://doi.org/10.1093/infdis/jiw235