Abstract

Interleukin-15 (IL-15) is a pleiotropic cytokine known to modulate both innate and adaptive immunity. It is suggested that IL-15 may play an important role in the regulation of immune response to hepatitis B virus (HBV). We investigated whether IL-15 could modulate the immune response to HBV. A mouse model for HBV tolerance was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. This HBV-carrier mouse was simultaneously hydrodynamically injected with either an IL-15-expression plasmid pLIVE-IL-15 or a mock control vector pLIVE-EGFP. The serum levels of HBsAg and HBeAg were measured by radioimmunoassay. Hydrodynamic injection of the plasmid pLIVE-IL-15 resulted in sustained high level of IL-15 in mouse serum, along with the markedly decreased serum HBsAg and HBeAg titres and liver HBV DNA levels. IL-15 also induced anti-HBV activity in T cell- and B cell-deficient Rag1(-/-) mice. Interestingly, despite an increase in NK cell numbers in both spleen and liver of IL-15 treated mice, the anti-HBV effect of IL-15 was neither dependent on presence of NK cells nor on production of IFN-γ. Furthermore, IL-15 could exert anti-HBV function independent of the common IL-2γ(c) R. Lastly, we found that IFN-β expression in the liver and serum was significantly up-regulated by liver expression of IL-15, and blockade of IFN-β function abrogated the anti-HBV activity of IL-15. Liver over-expression of IL-15 may suppress HBV replication in an IFN-β-dependent manner.

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