Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease

Abstract

Reactivation of latent herpes simplex virus type 1 (HSV-1) infection was induced by UV irradiation of the corneas of latently infected mice. On days 1--4 after stimulation, infectious virus was sought in nervous and ocular tissue. On days 4, 7 and 10, eyes with either recurrent epithelial or stromal disease and appropriate controls were stained to identify immune cells and HSV-1 antigens. The maximum incidence of infectious virus was on day 2 when 5/10 ophthalmic parts of the trigeminal ganglion yielded HSV. Thus in this mouse model, as in humans, reactivation of virus in the trigeminal ganglion is the likely source of virus producing recurrent disease and shedding in the tear film. On day 4, when virus antigens were still present, granulocytes were the predominant infiltrating cell in corneas with either type of disease. Small numbers ofT cells, dendritic cells and cells expressing MHC class II were also present. In stromal disease, the granulocyte infiltrate persisted and T cells remained sparse. In contrast, in epithelial disease, granulocyte numbers rapidly declined and both CD4 + and CD8 + T cells (present at a ratio of 1:1) increased significantly. The secondary immune response to virus antigen is more rapid and vigorous than that during primary corneal infection. Granulocytes may play a role in the initial clearance of virus, however, the other types of cells present early on provide the potential for a local secondary immune response. The high proportion of CD8 ÷ cells in epithelial disease compared with stromal disease suggests that they may be acting as suppressors.

Tracking the Spread of a lacZ -Tagged Herpes Simplex Virus Type 1 between the Eye and the Nervous System of the Mouse: Comparison of Primary and Recurrent Infection

“…In this case, however, the virus being transported is likely to be enveloped. Nevertheless, the chances of Schwann cells becoming infected may be low since only small amounts of virus appear to be produced as a result of reactivation (37) and the axon involved may be myelinated.…”

IL-17 Expression in Human Herpetic Stromal Keratitis: Modulatory Effects on Chemokine Production by Corneal Fibroblasts

“…These cellular interactions are assumed to result in the induction and perpetuation of a chronic inflammatory process resulting in corneal damage (2,3,7,8) activation of resident cells can be heavily modulated by the Th1-derived cytokine IL-17 (21)(22)(23)(24)(27)(28)(29)(30). Accordingly, the potential interactive role of IL-17 and corneal fibroblasts in the induction and perpetuation of inflammatory processes in human HSK was hypothesized.…”

“…In the preclinical phase, when HSV-1 replicates in the corneal epithelium, neutrophils invade the underlying corneal stroma (3). This transient response, triggered by replicating virus (4,5), is thought to control HSV replication and limit viral spread into peripheral tissues (6,7). During the second phase, i.e., the clinical phase, a second wave of inflammatory cells, predominantly consisting of neutrophils, infiltrates the corneal stroma (8).…”

A Recombinant Herpes Simplex Virus Type 1 Expressing Two Additional Copies of gK Is More Pathogenic than Wild-Type Virus in Two Different Strains of Mice

“…؉ T cells play a major role in HSV-1-mediated corneal pathogenesis (1,25,26,49). Furthermore, we have previously shown that the CS exacerbation in gK-immunized mice correlates with CD8 ؉ T cells, but not with CD4 ؉ T cells or macrophages (44).…”