Ocular exocrine glands are infected, harbor T cells, and express select cytokines and chemokines following corneal HSV-1 infection.

Abstract

Abstract Herpes simplex virus (HSV)-1 is a pathogen that infects a large portion of the human population and establishes a life-long, latent infection. Reactivation of HSV-1 can manifest as “cold sores” or more severe pathologies, including corneal herpes stromal keratitis. The potential involvement of ocular glands following corneal HSV-1 infection is not well described, despite their significant contribution to eye health. CD-1 outbred mice were ocularly infected with HSV-1, and ocular exocrine glands, including harderian glands (HGs) and extraorbital lacrimal glands (ELGs), were evaluated for susceptibility to infection and immunological activity. HSV-1 was found to infect ocular glands in a time-dependent fashion with HGs infected earlier than ELGs. Surgical removal of HGs prior to infection resulted in a significant increase in infectious virus recovered from corneas, but not ELGs or brainstems, when compared to mice with intact HGs (p≤0.01). Bidirectional flow was shown to occur between ocular surface contents and HGs in less than 4 hours, which might contribute to HSV-1 trafficking to HGs. CD4+ and CD8+ T cell infiltration/expansion occurs within HGs and ELGs in a time-dependent fashion post-infection (pi) compared to B cells that began to infiltrate HGs, but not ELGs, by day 5 pi. Cytokines, including IL-4, IL-6, IL-22, and IFN-γ, were found to be significantly (p≤0.05) elevated in ELGs, but not HGs, at day 7 pi. Chemokines, including CCL2, CCL5, and CXCL10, were significantly (p≤0.05) elevated in both ELGs and HGs at day 7 pi. These results underscore a dynamic response of ocular exocrine glands to corneal HSV-1 infection and the potential contribution these glands make to viral resistance.