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Published on: September 25, 2019
Tim-3 suppression combined with TLR3 activation enhances antiviral immune response in patients with chronic HCV
Yue-Min Nan1, Shan-Shan Su2, Xue-Min Niu2
1Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China nanyuemin@163.com.
Objective:
To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection.
Methods:
Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2'-5' oligoadenylate synthetase (2'-5'OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated.
Results:
Plasma Gal-9 levels were increased in patients (n = 52) compared with controls (n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2'-5'OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist.
Conclusions:
Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.
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