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

Sabine Vollstedt, Marco Franchini, Hans P. Hefti, Bernhard Odermatt, Meredith O'Keeffe, Gottfried Alber, Bettina Glanzmann, Matthias Riesen, Mathias Ackermann, Mark Suter

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65 Citations (Scopus)

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)-α/β 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-α/β- and IL-12-associated immune responses.

Original languageEnglish
Pages (from-to)575-584
Number of pages10
JournalJournal of Experimental Medicine
Volume197
Issue number5
DOIs
Publication statusPublished - 3 Mar 2003
Externally publishedYes

Keywords

  • Bacteria
  • DC
  • IL
  • Neonatal immune response
  • Virus

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