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Interleukin‐15 suppresses hepatitis B virus replication via IFN ‐β production in a C 57 BL /6 mouse model
Author(s) -
Yin Wenwei,
Xu Long,
Sun Rui,
Wei Haiming,
Tian Zhigang
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2012.02773.x
Subject(s) - hbsag , hepatitis b virus , hbeag , spleen , immune system , hepatitis b , immunology , interleukin 10 , biology , cytokine , interleukin 12 , virology , microbiology and biotechnology , virus , in vitro , cytotoxic t cell , biochemistry
Background 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 ). Aims We investigated whether IL ‐15 could modulate the immune response to HBV . Methods A mouse model for HBV tolerance was established by hydrodynamical injection of pAAV / HBV 1.2 plasmid into C 57 BL /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. Results 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 R ag1 −/− 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. Conclusions Liver over‐expression of IL ‐15 may suppress HBV replication in an IFN ‐β‐dependent manner.