The long-term but not the short-term antiviral effect of IFN-alpha depends on Flt3 ligand and pDC.
The cooperation between IFN-alpha/beta and FL, the ligand of Fms-like tyrosine kinase 3 (Flt3), plays an important role in the defense against herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFN-alpha has a short-term, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. The treatment of these mice with rIFN-alpha at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-alpha at birth induced both FL and plasmacytoid DC (pDC), resulting in enhanced resistance against HSV-1 at day 7. In contrast, in mice lacking FL, IFN-alpha treatment at birth did not influence the splenic cell composition and had no effect on viral protection. The transfer of pDC to mice lacking FL enhanced viral resistance. Therefore, the induction and function of pDC, normally controlled by IFN-alpha/beta and FL, are decisive for viral resistance in neonatal mice.
Vollstedt
Sabine
S
Institute for Virology, University of Zurich, Zurich, Switzerland.
O'Keeffe
Meredith
M
Ryf
Beat
B
Glanzmann
Bettina
B
Hochrein
Hubertus
H
Suter
Mark
M
D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000494:pharmacology*; D003713:Dendritic Cells / Q000502:physiology*; D006561:Herpes Simplex / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D000998:Antiviral Agents; D016898:Interferon-alpha; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein