PMID- 11298835
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 102
IP  - 3
DP  - 2001 Mar
TI  - Reduced herpes simplex virus type 1 latency in Flt-3 ligand-treated mice is 
      associated with enhanced numbers of natural killer and dendritic cells.
PG  - 352-8
AB  - We have investigated the effect of Flt-3 ligand (Flt-3L) on the resistance to 
      herpes simplex virus type-1 (HSV-1) infection in BALB/c mice which are normally 
      highly susceptible to challenge with this virus. We have confirmed data by others 
      that in vivo treatment with Flt-3L causes an increase in dendritic cells (DC) and 
      natural killer (NK) cells in lymphoid tissue. Increasing doses of Flt-3L caused a 
      corresponding increase in liver and spleen CD11c+ DC which were increased up to 
      20-fold compared with control levels. A significant expansion of NK cells was 
      seen in the spleen of Flt-3L-treated mice where the number of DX5+ cells was 
      increased by up to fivefold. We subsequently tested the hypothesis that Flt-3L 
      treatment, at the time of viral infection, might lead to enhanced immunity and 
      protection against viral pathogenesis. Two murine models of HSV-1 (SC16) 
      infection were used. In the first model, mice were injected with Flt-3L daily for 
      9 days. Control mice received mouse serum albumin (MSA). On day 7 of the Flt-3L 
      treatment 106 plaque-forming units (PFU) of SC16 was inoculated into the ear 
      pinna. Flt-3L treatment significantly reduced mortality following virus 
      inoculation, with 80% survivors in this group compared with 20% survivors in the 
      MSA-treated group. In the second model, Flt-3L-treated mice were scarified with 
      104 PFU of SC16. In this case there was 60% survival in the Flt-3L-treated group 
      of mice compared with 10% survival in the MSA-treated group. Assessment by in 
      situ hybridization for latency-associated transcripts showed that Flt-3L 
      treatment reduced the amount of latent virus within infected neurons. These 
      studies show that in vivo treatment with Flt-3L results in protection against 
      challenge with live HSV-1, which may be a consequence of enhanced numbers of DC 
      and/or NK.
FAU - Smith, J R
AU  - Smith JR
AD  - Centre for Veterinary Science, Department of Clinical Veterinary Medicine, 
      University of Cambridge, Madingley Road, Cambridge, UK.
FAU - Thackray, A M
AU  - Thackray AM
FAU - Bujdoso, R
AU  - Bujdoso R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Hematopoiesis/immunology
MH  - Herpes Simplex/immunology/*prevention & control/virology
MH  - Herpesvirus 1, Human/physiology
MH  - In Situ Hybridization
MH  - Killer Cells, Natural/*immunology
MH  - Ligands
MH  - Membrane Proteins/*therapeutic use
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neurons/virology
MH  - Survival Rate
MH  - Virus Latency/immunology
PMC - PMC1783181
EDAT- 2001/04/12 10:00
MHDA- 2001/05/22 10:01
PMCR- 2002/03/01
CRDT- 2001/04/12 10:00
PHST- 2001/04/12 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/12 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - imm1180 [pii]
AID - 10.1046/j.1365-2567.2001.01180.x [doi]
PST - ppublish
SO  - Immunology. 2001 Mar;102(3):352-8. doi: 10.1046/j.1365-2567.2001.01180.x.