May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
Aberrant Recruitment of CD11b+ and Gr–1+ Leukocytes Into the Cornea of CCR5 Deficient Mice Infected With HSV–1
Author Affiliations & Notes
  • D.J. Carr
    Ophthalmology, Univ Oklahoma HSC, Oklahoma City, OK
  • W. Kuziel
    Protein Design Labs, Inc., Fremont, CA
  • Footnotes
    Commercial Relationships  D.J. Carr, None; W. Kuziel, None.
  • Footnotes
    Support  NIH EY015566
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3544. doi:
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      D.J. Carr, W. Kuziel; Aberrant Recruitment of CD11b+ and Gr–1+ Leukocytes Into the Cornea of CCR5 Deficient Mice Infected With HSV–1 . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3544.

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

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Abstract: : Purpose: Ocular herpes simplex virus type 1 (HSV–1) infection elicits a robust inflammatory response that is associated with the ß chemokines CCL3 and CCL5, which share a common receptor, CCR5. The present investigation was undertaken to determine if the loss of CCR5 had an impact on the local host response measuring leukocyte recruitment and cytokine/chemokine production within the cornea of infected mice. Methods: Wild type (C57BL/6, 6–10 weeks old) and CCR5 knockout (CCR5–/–) mice were infected with HSV–1 (McKrae strain, 500 pfu/eye). At days 3–7 post infection (p.i.), the corneas of infected mice were collected and processed for CCL2, CCL3, CCL5, CXCL9, and CXCL10 levels by ELISA, virus titers by plaque assay, or CD11b+ cell recruitment by flow cytometry. In addition, the infiltration of Gr–1+ cells and the local expression of CCL5 and CCR5 relative to HSV–1 antigen expression were measured in corneal flat mounts by confocal microscopy. Results: HSV–1 titers were nearly identical comparing the wild type (WT) to CCR5–/– mice for the first 5 days p.i. However, by day 7 p.i., infectious virus recovered from the corneas of CCR5–/– mice contained over a log more virus compared to the WT controls (4.3 vs. 3.2 log10), p<.05 determined by ANOVA and Scheffé multiple comparison test. There were no significant differences in the level of any of the chemokines expressed in the cornea comparing the two groups of mice. However, consistent with flow cytometry data that showed an initial reduction in the trafficking of CD11b+ cells into the cornea of the CCR5–/– mice, the recruitment of Gr–1+ cells into the cornea of CCR5–/– mice was also restricted during the first 3 days p.i. By day 5 p.i. similar levels of Gr–1+ cells were observed but the cells from the CCR5–/– mice were restricted to the stroma whereas cells from the WT mice were present in the stroma as well as the epithelial layers of the cornea. Co–localization of CCL5 and HSV–1 antigen was observed in the epithelium as well as the stroma following virus infection. However, CCL5 was also found expressed in tissue absent of HSV–1 antigen or infiltrating Gr–1+. CCL5 was not detected in uninfected cornea. WT mice did not express CCR5 in the cornea prior to or after infection. However, CCR5 was expressed in the draining (cervical) lymph nodes of infected mice. Conclusions: The absence of CCR5 had a modest effect on the host response to ocular HSV–1 infection. This effect is indirect and may reflect changes in the trafficking patterns of leukocytes from the draining lymph nodes as well as other sites.

Keywords: cytokines/chemokines • herpes simplex virus • transgenics/knock-outs 

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