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kai Hu, Ulrich H. von Andrian, Pedram Hamrah; Infection of the Cornea with Herpes Simplex Virus-1 Results in Immediate Destruction of Subbasal Corneal Nerves and Increased Density and Maturation of Corneal Antigen-Presenting Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5796.
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Patients with herpes simplex keratitis (HSK) demonstrate decreased corneal nerve density within days of infection, resulting in loss of sensation. During HSK, herpes simplex virus (HSV)-1spreads to the trigeminal ganglion (TG) through retrograde travel in corneal nerves. To date, little is known about the early pathogenesis of host-pathogen interaction in HSK. The purpose of this study was to investigate early nerve destruction, as well as related immune responses in HSK.
C57BL/6 mice were infected by ocular inoculation with HSV-1 McKrae, while control mice were inoculated with virus medium. Corneas were excised at days 1, 2, and 3 after inoculation and immunofluorescence staining with antibodies against HSV-1, β-Tubulin, CD11c, CD11b, MHC-II was performed by confocal microscopy on whole-mounted corneas.
As early as 24 h post infection (PI), initial focal destruction of the subbasal nerves was noted below infected epithelial cells. On day 3 PI, the subbasal nerve plexus was completely destroyed in the infected areas with only few nerves left. The central subbasal nerve density on day 1, 2 and 3 PI were 64000±8970µm/mm2, 14800±3400µm/mm2 and 1450±530µm/mm2 respectively, which was significantly decreased as compared to control mice (124500±46370µm/mm2)(p<0.01, p<0.0001, p<0.0001). On day 1 PI, corneal nerves started to get infected by HSV-1. Interestingly, all infected nerves were located peripherally. Concomitant with nerve destruction, there was a significant increase in CD11c+ and CD11b+ cells both in the central (167±35 cells/mm2, 413±65 cells/mm2) and peripheral (467±81 cells/mm2, 873±95 cells/mm2) cornea, as compared to central (67±11cells/mm2, 247±72cells/mm2) (p<0.001, p<0.05) and peripheral (207±23cells/mm2, 280±87cells/mm2) (p<0.01, p<0.001) normal corneas. Moreover, there was significant increase in MHC-II expression on CD11c+ and CD11b+ cells (p<0.01) throughout the cornea.
Subbasal cornea nerves are destroyed extensively, immediately after infection with HSV-1. HSV-1 can only be observed in peripheral corneal nerves from day 1 PI, but not centrally. The destruction of corneal nerves is accompanied with the significant increase and maturation of corneal antigen-presenting cells.
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