Herpes simplex virus type 1-mediated up-regulation of IL-12 (p40) mRNA expression. Implications in immunopathogenesis and protection.

Abstract

In this report we investigated whether induction of IL-12 occurs in response to herpes simplex virus (HSV) infection of the mouse eye, which may serve to regulate the nature of the subsequent immune response. The data show early induction and continued maintenance of IL-12 (p40) mRNA in the cornea and draining lymph node upon ocular infection with HSV. Using a very sensitive radioimmunoassay technique, IL-12 (p40) protein also was detected in the cornea upon ocular HSV infection. Unfractionated splenocytes and enriched populations of dendritic cells, macrophages, and neutrophils all responded to HSV infection in vitro by up-regulating the expression of IL-12 (p40) mRNA. However, cultured corneal cells failed to generate IL-12 (p40) upon exposure to HSV. The data indicate that inflammatory cells that infiltrate the cornea in response to HSV-1 infection are the main source of IL-12 in the eye. Our results are consistent with the hypothesis that IL-12 induction in the eye acts as a triggering event that biases HSV-specific immunity to a type 1 T cell response, which, in the environment of the eye, culminates in an immunopathologic disease.