Pattern recognition receptor responses in children with chronic hepatitis B virus infection

Abstract

Background: Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children, since 90% of children become chronic carriers compared to 5% of adults when infected with HBV.

Objectives: We wanted to study the function of TLRs and cytosolic DNA receptors in children with CHB infection compared to healthy children.

Study design: PBMCs from 19 children with CHB and 19 healthy children were stimulated with ligands for TLR 2, 3, 4, 7 and 9 for 24 h. For activation of cytosolic DNA receptors, cells were transfected with a double-stranded DNA using Lipofectamine 2000. Supernatants were analyzed for levels of IFN-α, TNF-α, IL-6, CXCL10 and CCL3 by Luminex.

Results: Stimulation with ligands for TLR2, TLR3 and TLR9 induced IL-6, CCL3 and CXCL10 to a significantly higher level in children with CHB compared to healthy children. CHB patients displayed significantly lower IFN-α production compared to healthy children after stimulation with ligands for TLR2, TLR3 and TLR4. Stimulation of intracellular DNA sensors with synthetic double-stranded DNA elicited significantly higher induction of the inflammatory cytokines and chemokines IL-6, TNF-α and CCL3 in the CHB patients as compared to the healthy children.

Conclusions: Our results indicate a TLR-mediated inflammatory response in children with CHB infection. Furthermore, our study is the first to show that the responses of intracellular DNA receptors are affected in CHB.