June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Resident Corneal Plasmacytoid Dendritic Cells Prevent Clinical Manifestations of Primary Herpes Simplex Virus-1 Keratitis
Author Affiliations & Notes
  • Victor G Sendra
    Ophthalmology, Center for Translational Ocular Immunology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Gustavo Ortiz
    Ophthalmology, Center for Translational Ocular Immunology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Arsia Jamali
    Ophthalmology, Center for Translational Ocular Immunology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Pedram Hamrah
    Ophthalmology, Center for Translational Ocular Immunology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
    Ophthalmology, Cornea Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Victor Sendra, None; Gustavo Ortiz, None; Arsia Jamali, None; Pedram Hamrah, None
  • Footnotes
    Support  NIH-R01- EY022695, NIH R21-EY025393, Research to Prevent Blindness Challenge grant, Massachusetts Lions Eye Research Fund, Inc., Tufts Medical Center Institutional Support
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 437. doi:
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    • Get Citation

      Victor G Sendra, Gustavo Ortiz, Arsia Jamali, Pedram Hamrah; Resident Corneal Plasmacytoid Dendritic Cells Prevent Clinical Manifestations of Primary Herpes Simplex Virus-1 Keratitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):437.

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

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Abstract

Purpose : Plasmacytoid dendritic cells (pDCs), are specialized cells of the immune system that reside in the cornea. Herein, we evaluate the role of resident corneal pDCs in mediating clinical keratitis during asymptomatic primary herpes simplex virus (HSV)-1 keratitis

Methods : Corneal HSV-1 infection was induced by inoculation of either 10^3 (low-dose) or 10^5 (high-dose) PFU/eye of HSV-1 strain McKrae in scarified corneas in BDCA-2-DTR Tg mice, prior to pDCs depletion by subconjunctival (s.conj.) diphtheria toxin (DT) injections. Clinical corneal opacity was scored on a 0-4 scale. Corneas and trigeminal ganglia (TG) were excised for viral glycoprotein B mRNA quantification by qRT-PCR. Adoptive transfer of pDCs were performed with 10^4 sorted pDCs transferred to debrided corneas by using fibrin sealant 24h before HSV-1 infection in sham and pDC-depleted corneas

Results : At 3 days post-inoculation (dpi) with low-dose challenge, clinical assessment of corneas of sham- and pDC-depleted mice revealed a marked difference in corneal opacification (0.3 vs. 1.5, p=0.009) respectively, while at high-dose opacity was more severe in pDC-depleted corneas (0.8 vs. 2.4, p<0.001). At 5 dpi, corneal opacity was apparent in all pDC-depleted mice, but only in 25% of sham-depleted controls (0.7 vs 2.7, p=0.004), presenting clinically with less severe keratitis and reduced viral mRNA in the corneal stroma (1.2 vs. 5.2, p=0.036), and in the TG compared to pDC-depleted mice (6.6 vs. 717.0, p=0.015). A 6.6-time fold increased gB RNA in TG in low-dose HSV-1 infected corneas was noticed. Next, adoptive transfer of pDCs was performed in pDC-depleted mice prior to HSV-1 infection in order to restore a resident corneal pDC population. At 3 dpi, corneas with repopulated pDCs showed a lower clinical severity compared to pDC-depleted corneas (0.5 vs. 1.5, p=0.037)

Conclusions : Our data shows that resident corneal pDCs prevent clinical manifestations in primary HSV-1 infection of the cornea, by controlling HSV-1 replication and spread to the TG. The results further suggest that HSV-1 can travel to TG despite lack of corneal clinical manifestation . Restoring resident corneal pDCs by adoptive transfer improves clinical severity in HSV-1 infected mice, suggesting a pivotal role of pDCs in the clinical outcomes during primary HSV-1 infection

This is a 2020 ARVO Annual Meeting abstract.

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