The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published 3 March 2003. doi:10.1084/jem.20021900
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© Rockefeller University Press, 0022-1007/2003/3/575 $5.00
The Journal of Experimental Medicine, Volume 197, Number 5, 575-584

Flt3 Ligand–treated Neonatal Mice Have Increased Innate Immunity Against Intracellular Pathogens and Efficiently Control Virus Infections

Sabine Vollstedt1, Marco Franchini1, Hans P. Hefti1, Bernhard Odermatt2, Meredith O'Keeffe3, Gottfried Alber4, Bettina Glanzmann1, Matthias Riesen1, Mathias Ackermann1 and Mark Suter1

1 Institute of Virology, University of Zurich, 8057 Zurich, Switzerland
2 Institute of Pathology, University of Zurich, 8057 Zurich, Switzerland
3 The Walter and Eliza Hall Institute of Medical Research, 3050 Melbourne, Australia
4 Institute of Immunology, University of Leipzig, D-04109 Leipzig, Germany

Address correspondence to Mark Suter, Institute of Virology, University of Zurich, Winterhurerstr. 266a, 8057 Zurich, Switzerland. Phone: 41-1-635-8717; Fax: 41-1-635-8911; E-mail: msuter{at}vetvir.unizh.ch

Flt-3 ligand (FL), a hematopoetic growth factor, increases the number of dendritic cells (DCs), B cells, and natural killer cells in adult mice but the effect in neonates was unknown. We show that FL treatment of newborn mice induced a >100-fold increase in the innate resistance against infection with herpes simplex virus type 1 and Listeria monocytogenes. This resistance required interferon (IFN)-{alpha}/ß for viral and interleukin (IL)-12 for bacterial infections. Long-term survival after viral but not bacterial infection was increased ~100-fold by FL treatment. After treatment, CD11c+/major histocompatibility complex type II+ and CD11c+/B220+ DC lineage cells were the only cell populations increased in the spleen, liver, peritoneum, and skin. DC induction was independent of IFNs, IL-2, -4, -7, -9, -15, and mature T and B cells. The data suggest that FL increases the number of DCs in neonates and possibly in other immune-compromised individuals, which in turn improves IFN-{alpha}/ß– and IL-12–associated immune responses.

Key Words: neonatal immune response • DC • IL • virus • bacteria


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