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 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.
Vollstedt
Sabine
S
Institute of Virology, University of Zurich, 8057 Zurich, Switzerland.
Franchini
Marco
M
Hefti
Hans P
HP
Odermatt
Bernhard
B
O'Keeffe
Meredith
M
Alber
Gottfried
G
Glanzmann
Bettina
B
Riesen
Matthias
M
Ackermann
Mathias
M
Suter
Mark
M
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D015996:Survival Rate
D018398:Homeodomain Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; C084881:flt3 ligand protein; C064658:RAG-1 protein; D018664:Interleukin-12; D016899:Interferon-beta