High Frequency of IFN-g-Producing PLZF^lo RORgt^lo iNKT1 Cells Infiltrating HSV-1 Infected Cornea is Associated with Protection from Ocular Herpes Infection and Disease

Abstract

Purpose : The invariant natural killer (iNKT) cells are among the first innate immune cells to elicit early protective immunity that control invading viral pathogens. The role of iNKT cells and of their three major subsets, iNKT1, iNKT2, and iNKT17, in herpes immunity remains to be fully elucidated. In this study, we examined the protective role of corneal-resident iNKT cell subsets, using the mouse model of ocular herpes infection and disease.

Methods : Wild type (WT) C57BL/6 mice and CD1d knockout (KO) mice were infected ocularly with HSV-1 (strain McKrae). Cornea, spleen and liver were harvested at 2, 5, 8 and 14-days post-infection (p.i.) and the frequency and function of the three major iNKT cell subsets were analyzed by immunostaining and flow cytometry. The profiles of sixteen major cytokines were analyzed in corneal lysates using western blot and Luminex assays.

Results : Early during ocular herpes infection (i.e. day 2), the PLZF^lo RORgt^lo iNKT1 cell subset, was the predominate iNKT cell subset in the infected asymptomatic corneas. Asymptomatic mice (with reduced corneal herpetic disease) had more functional IFN-g-producing PLZF^lo RORgt^lo iNKT1 cells, compared to symptomatic mice. Moreover, compared to HSV-1 infected WT mice, the CD1d KO mice, with iNKT cell deficiency, are more susceptible to HSV-1 ocular infection and disease. This was associated with a decrease in: (i) IFN-γ production, and (ii) activation of MAPK (ERK1/2) and NFkB pathways in the cornea.

Conclusions : Our findings suggest that the IFN-γ-producing PLZF^lo RORgt^lo iNKT1 cells play a protective role against ocular herpes.

This is a 2021 ARVO Annual Meeting abstract.