June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
A STING-dependent innate sensing pathway mediates resistance to corneal HSV-1 infection
Author Affiliations & Notes
  • Derek J Royer
    Microbiology & Immunology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK
  • Daniel J Carr
    Microbiology & Immunology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK
    Ophthalmology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK
  • Footnotes
    Commercial Relationships Derek Royer, None; Daniel Carr, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 939. doi:
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      Derek J Royer, Daniel J Carr; A STING-dependent innate sensing pathway mediates resistance to corneal HSV-1 infection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):939.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Type 1 interferons (IFN-α/β) mediate host resistance to herpes simplex virus type 1 (HSV-1) infection in the cornea. Our lab has previously shown that the loss of toll-like receptor (TLR) signaling does not affect host resistance to HSV-1 in the cornea; rather, a TLR-independent pathway drives the production of IFN-α/β at day 2 post infection (pi) through the cytosolic innate sensor adaptor protein, the stimulator of interferon genes (STING). We hypothesized that STING also mediates host resistance to corneal HSV-1 infection and preserves the corneal integrity through day 5 pi via the induction of IFN-α/β.

Methods: In the current study, wildtype (WT), STING-deficient (STING-/-), and IFN-α/β receptor deficient (CD118-/-) mice were infected with HSV-1. Corneal viral burden at day 5 pi was assessed by plaque assay, edema monitored with a pachymeter, and infiltrating cells characterized via flow cytometry. Corneal whole mounts were prepared to visualize lymphatic vessels and mast cells by confocal microscopy.

Results: STING-/- and CD118-/- mice had comparable corneal HSV-1 titers that were both significantly higher than WT at day 5 pi. However, the increase in viral titer did not directly correlate with tissue edema or infiltrating leukocytes. Corneal edema was unremarkable in WT and STING-/- corneas through day 5 pi despite the difference in viral burden, while CD118-/- corneas exhibited substantial edema beginning on day 3 pi. Edema was independent of leukocyte infiltration, as similar numbers of total leukocytes and specifically neutrophils were observed in STING-/- and CD118-/- corneas at day 5 pi. Preliminary evidence supports a role for the lymphatic vasculature surrounding the cornea in regulating corneal edema, as the lymphatic vessels and limbal mast cells are lost by day 5 pi in CD118-/- corneas but not in WT or STING-/- corneas.

Conclusions: Consistent with the hypothesis, our results support a role for STING in innate host resistance to HSV-1 infection with respect to viral surveillance and containment within the corneal microenvironment. However, auxiliary STING-independent, IFN-α/β-dependent pathways are necessary to limit corneal edema attributed here to the loss of lymphatic vessels surrounding the tissue. Furthermore, our results suggest that limbal mast cells preserve and protect the lymphatic vasculature via auxiliary IFN-α/β-dependent pathways.


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