γδ T17 cells are master regulators of the acute antiviral response in HSV-1 infected corneas

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1006
Abstract ID: 5605

Presenting Author:
Rachel Rodenberg , graduate student at Univ. of South Alabama Whiddon Col. of Med.

Abstract:

Herpes stromal keratitis (HSK), caused by herpes simplex virus 1 (HSV-1), is the leading cause of infectious blindness in developed countries. Innate-acting γδ T17 cells are critical for protection against ocular HSV-1 infection. It is well established these cells can facilitate neutrophil influx into the cornea, but whether γδ T17 cells regulate other innate immune cells following ocular HSV-1 infection remains unclear. Natural killer (NK) cells also participate in the innate immune response generated against HSV-1 by directly killing infected cells through secretion of granzymes and promoting the antiviral response by production of IFN-γ. Our data strongly suggest that γδ T17 cell secretion of IL-17A promotes NK cell accumulation in the infected cornea. This is demonstrated in several ways: 1) in mice that lack γδ T cells (TCRδ^-/-) there are fewer antiviral NK cells following corneal HSV-1 infection compared to wild-type (WT) mice; 2) administering IL-17A to TCRδ^-/- mice restored the NK cell population; and 3) neutralization of IL-17A or 4) inhibiting γδ T17 cell influx to corneas in WT mice diminished NK cell accumulation leading to increased viral titers. In contrast, IL-17A production is enhanced in the absence of IFN-γ.  In sum, this study identifies a novel mechanism by which IL-17A production by γδ T17 cells promotes antiviral NK cell responses that, in turn limit further IL-17A production via INF-γ secretion by NK cells in the HSV-1 infected cornea.