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Reduced herpes simplex virus type 1 latency in Flt‐3 ligand‐treated mice is associated with enhanced numbers of natural killer and dendritic cells
Author(s) -
Smith J. R.,
Thackray A. M.,
Bujdoso R.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01180.x
Subject(s) - herpes simplex virus , spleen , cd11c , biology , virus , immunology , in vivo , pathogenesis , virology , phenotype , biochemistry , microbiology and biotechnology , gene
Summary 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 10 6 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 10 4 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.