Abstract
Abstract The innate immune response represents the host's first line of defense to infection. The toll-like receptors (TLRs) are a family of pattern recognition receptors triggered by specific pathogen-associated molecular patterns (PAMPs). To examine the role of TLRs in a mouse model of viral encephalitis, mice with defects in TLR-2, TLR-3 or TLR-4 were intracerebrally infected with Theiler's murine encephalomyelitis virus (TMEV) to determine the impact of TLR deletion on the extent of disease. At day 16 post-infection, a timepoint when limited pathology is observed in TMEV-infected wild-type control animals, extensive brain pathology was observed in TLR-2 and TLR-3 knockout mice. While pathology was observed in TLR-4 knockout mice following TMEV infection, the pathology was less than that observed in the TLR-2 and TLR-3 knockout animals. TLR-4 knockout mice mounted more robust antibody responses to TMEV the other strains of mice, suggesting that this mechanism of virus clearance may account for the reduced level of pathology observed in these animals. Support: National Multiple Sclerosis Society (RG3870A3); Department of Defense (PR064574)