IFN-α production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and -independent pathways

Understanding the defense mechanisms of the host of an organism is important for infection control. In previous studies, we demonstrated that interferon-alpha (IFN-alpha), but not IL-12, was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus (VZV). Here, we investigated what kind of cell(s) and which signal molecule(s) are involved in IFN-alpha production. Using cell isolation and ELISA, we found that plasmacytoid dendritic cells (pDCs) were responsible for IFN-alpha production during VZV infection. We also found that Toll-like receptor 9 (TLR9) was involved in VZV-induced IFN-alpha production because inhibitory CpG oligodeoxynucleotide inhibited IFN-alpha production. UV-inactivated VZV-induced IFN-alpha production was lower than that of active VZV, indicating another TLR9-independent pathway. Further studies demonstrated that double-stranded RNA-dependent protein kinase, but not DNA-dependent protein kinase was involved in VZV-induced IFN-alpha production. Together, these results suggest that pDCs play an important role in IFN-alpha production during VZV infection through TLR9-dependent and -independent pathways. Cellular & Molecular Immunology (2011) 8, 181-188; doi:10.1038/cmi.2010.84; published online 14 February 2011