Flt3 ligand-treated neonatal mice have increased innate immunity against intracellular pathogens and efficiently control virus infections

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...

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Veröffentlicht in:The Journal of experimental medicine Jg. 197; H. 5; S. 575
Hauptverfasser: Vollstedt, Sabine, Franchini, Marco, Hefti, Hans P, Odermatt, Bernhard, O'Keeffe, Meredith, Alber, Gottfried, Glanzmann, Bettina, Riesen, Matthias, Ackermann, Mathias, Suter, Mark
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 03.03.2003
Schlagworte:
Animals
Animals, Newborn
B-Lymphocytes - metabolism
Dendritic Cells - immunology
Dendritic Cells - metabolism
Flow Cytometry
Herpes Simplex - immunology
Herpesvirus 1, Human
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Immunity, Innate
Interferon-alpha - metabolism
Interferon-beta - metabolism
Interleukin-12 - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Listeria monocytogenes
Listeriosis - immunology
Membrane Proteins - pharmacology
Mice
Mice, Inbred Strains
Mice, Knockout
Skin - cytology
Skin - metabolism
Spleen - cytology
Spleen - metabolism
Survival Rate
ISSN:0022-1007
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-1007
DOI:10.1084/jem.20021900