hbsag Inhibits TLR2 Ligand-Induced IL-12 in Monocytes/Macrophages
J Immunol. 2013 Apr 12. [Epub ahead of print]
Hepatitis B Virus Surface Antigen Selectively Inhibits TLR2 Ligand-Induced IL-12 Production in Monocytes/Macrophages by Interfering with JNK Activation.
Wang S, Chen Z, Hu C, Qian F, Cheng Y, Wu M, Shi B, Chen J, Hu Y, Yuan Z.
Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai 200032, China;
It is widely accepted that chronic hepatitis B virus (HBV) infection is the result of an ineffective antiviral immune response against HBV infection. Our previous study found that the hepatitis B surface Ag (HBsAg) was related to decreased cytokine production induced by the TLR2 ligand (Pam3csk4) in PBMCs from chronic hepatitis B patients. In this study, we further explored the mechanism involved in the inhibitory effect of HBsAg on the TLR2 signaling pathway. The results showed that both Pam3csk4-triggered IL-12p40 mRNA expression and IL-12 production in PMA-differentiated THP-1 macrophage were inhibited by HBsAg in a dose-dependent manner, but the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α was not influenced. The Pam3csk4-induced activation of NF-κB and MAPK signaling were further examined. The phosphorylation of JNK-1/2 and c-Jun was impaired in the presence of HBsAg, whereas the degradation of IκB-α, the nuclear translocation of p65, and the phosphorylation of p38 and ERK-1/2 were not affected. Moreover, the inhibition of JNK phosphorylation and IL-12 production in response to Pam3csk was observed in HBsAg-treated monocytes/macrophages (M/MΦs) from the healthy donors and the PBMCs and CD14-positive M/MΦs from chronic hepatitis B patients. Taken together, these results demonstrate that HBsAg selectively inhibits Pam3csk4- stimulated IL-12 production in M/MΦs by blocking the JNK-MAPK pathway and provide a mechanism by which HBV evades immunity and maintains its persistence.
Well done research that used surface antigen concentrations that are expected in chronic patients. 1, 5, and 25 microgram/ml, which is approx equivalent to 1000iU, 5000, and 2500 iU/ml.
At 1 ug/ml there was almost no neg effect on Il-12 production, at 5 there was an approx 30% decrease and up to 80% less Il-12 was produced in the presence of 25 ug/ml. Overall this points to yet another mechanism by which high surface antigen impairs the generation of an effective Tcell response of the Th-1 kind, which mainly focuses on CTL production and ultimately gamma interferon release to clear cccDNA from infected hepatocytes.
This site complies with the HONcode standard for trustworthy health information.
The Content on this Site is presented in a summary fashion, and is intended to be used for educational and entertainment purposes only. It is not intended to be and should not be interpreted as medical advice or a diagnosis of any health or fitness problem, condition or disease; or a recommendation for a specific test, doctor, care provider, procedure, treatment plan, product, or course of action. Med Help International, Inc. is not a medical or healthcare provider and your use of this Site does not create a doctor / patient relationship. We disclaim all responsibility for the professional qualifications and licensing of, and services provided by, any physician or other health providers posting on or otherwise referred to on this Site and/or any Third Party Site. Never disregard the medical advice of your physician or health professional, or delay in seeking such advice, because of something you read on this Site. We offer this Site AS IS and without any warranties. By using this Site you agree to the following Terms and Conditions. If you think you may have a medical emergency, call your physician or 911 immediately.