Reduced herpes simplex virus type 1 latency in Flt-3 ligand-treated mice is associated with enhanced numbers of natural killer and dendritic cells.
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.
Smith
J R
JR
Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, UK.
Thackray
A M
AM
Bujdoso
R
R
D000818:Animals; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006410:Hematopoiesis / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000821:virology; D015996:Survival Rate; D017735:Virus Latency / Q000276:immunology
D008024:Ligands; D008565:Membrane Proteins; C084881:flt3 ligand protein