TY - JOUR
T1 - The long-term but not the short-term antiviral effect of IFN-α depends on Flt3 ligand and pDC
AU - Vollstedt, Sabine
AU - O'Keeffe, Meredith
AU - Ryf, Beat
AU - Glanzmann, Bettina
AU - Hochrein, Hubertus
AU - Suter, Mark
PY - 2006/5
Y1 - 2006/5
N2 - The cooperation between IFN-α/β 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-α 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-α at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-α 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-α 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-α/β and FL, are decisive for viral resistance in neonatal mice.
AB - The cooperation between IFN-α/β 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-α 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-α at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-α 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-α 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-α/β and FL, are decisive for viral resistance in neonatal mice.
KW - Flt3-L
KW - Interferon
KW - Newborn
KW - Resistance
KW - Virus
UR - http://www.scopus.com/inward/record.url?scp=33646546383&partnerID=8YFLogxK
U2 - 10.1002/eji.200535759
DO - 10.1002/eji.200535759
M3 - Article
C2 - 16639711
AN - SCOPUS:33646546383
VL - 36
SP - 1231
EP - 1240
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 5
ER -