Inflammatory responses elicited by ocular herpes simplex virus type 1 infection are inhibited by upregulation of programmed cell death ligand 1 on trigeminal ganglionic neurons (50.29)

Abstract

Abstract T cell effector responses are required for clearance of viral infection. In locations such as the central and peripheral nervous systems, where cell types lack regenerative ability, it is also critical that protective T cell responses produce minimal collateral damage. Using a murine model of ocular herpes simplex virus type 1 (HSV-1) infection, we report that programmed cell death ligand 1 (PD-L1) expression by trigeminal ganglia (TG) neurons is dramatically upregulated during acute infection, and that this increased PD-L1 expression is regulated by local expression of gamma-interferon. We further observed that treatment with anti-PD-L1 antibody significantly increased the overall number of CD4+ and CD8+ T cells as well as the number of HSV-specific CD8+ T cells present in the TG during acute infection. Anti-PD-L1 antibody treatment also affected T cell activation status as increased granzyme B expression was detected in all three of these T cell populations. Although control of viral replication in the TG appeared to be unaffected by treatment, during acute infection TG neurons from mice treated with anti-PD-L1 antibody became susceptible to perforin-mediated killing. Together, our data demonstrate a novel neuroprotective role for PD-L1 during acute viral infection, and may also suggest avenues for development of therapies capable of inhibiting the neuronal damage associated with many inflammatory conditions.