Effect of pretreatment with toll-like receptor agonists in a mouse model of herpes simplex virus type 1 encephalitis.

ABSTRACT

BACKGROUND: We evaluated the effect of pretreatment with Toll-like receptor (TLR) agonists in a mouse model of herpes simplex virus type 1 (HSV-1) encephalitis. METHODS: BALB/c mice received a single intraperitoneal or intranasal injection of polyinosinicpolycytidylic acid (poly IC), a TLR3 agonist; lipopolysaccharide (LPS), a TLR4 agonist; oligodeoxynucleotide (ODN), a TLR9 agonist; or control vehicle. Twenty-four hours later, animals were infected with 5000 plaque-forming units of HSV-1. RESULTS: Mice that received intraperitoneal pretreatment with vehicle, LPS, and poly IC had survival rates of 7%, 13%, and 56%, respectively, and mean life expectancies of 156.80+/-9.56, 176.00+/-9.24, and 213.00+/-7.71 h, respectively (p< .05, poly IC group vs. other groups). Similarly, intranasal pretreatment with vehicle, LPS, ODN, and poly IC were associated with survival rates of 20%, 47%, 60%, and 94%, respectively, and mean life expectancies of 153.60+/-11.71, 188.80+/-12.97, 204.80+/-11.73, and 234.00+/-5.81 h, respectively (p< .05, ODN and poly IC groups vs. vehicle group). Pretreatment with intranasal poly IC induced early expression of several immune genes in the brain and resulted in a significantly lower virus load. CONCLUSION: TLR3 stimulation by poly IC 24 h before infection reinforces a natural innate immune mechanism of neuroprotection against HSV-1.