Skip to main content

Free Content PD-1 negatively regulates interleukin-12 expression by limiting STAT-1 phosphorylation in monocytes/macrophages duringchronic hepatitis C virus infection

Download Article:

You have access to the full text article on a website external to ingentaconnect.

Please click here to view this article on Wiley Online Library.

You may be required to register and activate access on Wiley Online Library before you can obtain the full text. If you have any queries please visit Wiley Online Library

Abstract:

Summary

Hepatitis C virus (HCV) is remarkably efficient at evading host immunity to establish chronic infection. During chronic HCV infection, interleukin-12 (IL-12) produced by monocytes/macrophages (M/M) is significantly suppressed. Programmed death-1 (PD-1), an inhibitory receptor on immune cells, plays a pivotal role in suppressing T-cell responses during chronic viral infection. To determine whether PD-1 regulates IL-12 production by M/M during chronic HCV infection, we examined the expressions of PD-1, its ligand PDL-1, and their relationship with IL-12 production in M/M from HCV-infected, HCV-resolved, and healthy subjects by flow cytometry. Toll-like receptor (TLR) -mediated IL-12 production by M/M was selectively suppressed, while PD-1/PDL-1 expressions were up-regulated, in HCV-infected subjects compared with HCV-resolved or healthy subjects. Up-regulation of PD-1 was inversely associated with the degree of IL-12 inhibition in HCV infection. Interestingly, the reduced response of M/M from HCV-infected individuals to TLR ligands appeared not to be the result of a lack of the ability to sense pathogen, but to an impaired activation of intracellular janus kinase/signal transducer and activator of transfection (STAT) pathway as represented by inhibited STAT-1 phosphorylation in M/M from HCV-infected individuals compared with HCV-negative subjects. Successful HCV treatment with pegylated interferon/ribavirin or blocking PD-1/PDL-1 engagement ex vivo led to reduced PD-1 expression and improved IL-12 production as well as STAT-1 activation in M/M from HCV-infected individuals. These results suggest that the PD-1 inhibitory pathway may negatively regulate IL-12 expression by limiting STAT-1 phosphorylation in M/M during chronic HCV infection.

Keywords: Immune regulation; hepatitis C virus infection; interleukin-12; macrophages; programmed death-1

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2567.2010.03382.x

Affiliations: 1: Division of Infectious Diseases, Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA 2: Medical Service, Department of Veterans Affairs, James H. Quillen VA Medical Center, Johnson City, TN, USA

Publication date: March 1, 2011

bsc/imm/2011/00000132/00000003/art00012
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more