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J Exp Med ; 197(5): 575-84, 2003 Mar 03.
Article in English | MEDLINE | ID: mdl-12615899

ABSTRACT

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/beta for viral and interleukin (IL)-12 for bacterial infections. Long-term survival after viral but not bacterial infection was increased approximately 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/beta- and IL-12-associated immune responses.


Subject(s)
Herpes Simplex/immunology , Herpesvirus 1, Human , Immunity, Innate , Listeria monocytogenes , Listeriosis/immunology , Membrane Proteins/pharmacology , Animals , Animals, Newborn , B-Lymphocytes/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Flow Cytometry , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Interferon-alpha/metabolism , Interferon-beta/metabolism , Interleukin-12/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Mice , Mice, Inbred Strains , Mice, Knockout , Skin/cytology , Skin/metabolism , Spleen/cytology , Spleen/metabolism , Survival Rate
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