Abstract
Abstract: :
Purpose:Out of six chemokines surveyed including MIP–1α (CCL3), MIP–2 (CXCL1), MCP–1 (CCL2), RANTES, (CCL5), Mig (CXCL9), and IP–10 (CXCL10) only CXCL10 is constitutively detected in the cornea by ELISA (15–20 pg/cornea). Within the first 24 hour post HSV–1 infection, CXCL10 levels have significantly risen above the basal level. Blocking the expression of CXCL10 using a neutralizing antibody results in a transient rise in HSV–1 titers in the eye and trigeminal ganglion (TG) of infected mice during acute infection. These initial observations led us to propose that CXCL10 expression is central to efficient viral clearance from the host. To test this hypothesis, mice lacking the receptor for CXCL10, referred to as CXCR3–/– mice, were compared to wild type mice in their response to ocular HSV–1 infection. Methods:Wild type (C57BL/6, 6–10 weeks old) (n=19) and CXCR3 knockout (CXCR3–/–) (n=10) mice were infected with HSV–1 (McKrae strain, 500 pfu/eye). Viral titers were measured by plaque assay from the cornea, iris, retina, TG, and brain stem (BS) at day 7 post infection (p.i). The level of selective chemokines (including CCL3, CCL5, CXCL9, and CXCL10) as well as interferon–gamma in the infected tissue was measured by ELISA as well. Results:In evaluating viral titers in the infected mice, the iris, retina, TG, and BS of the CXCR3–/– mice showed significantly elevated levels compared to the wild type mice. Viral loads were not significantly different in the cornea comparing the two groups of mice. Similar to previous results, the iris possessed the greatest viral load of any tissue surveyed in both the wild type and CXCR3–/– mice. Viral loads in the BS correlated with selective cytokine/chemokine levels. Specifically, CCL5, CXCL9, CXCL10, and interferon–gamma were elevated in the BS of the CXCR3–/– mice compared to wild type controls. Conclusions:The presence of CXCR3 expression optimizes the host response in clearing virus infection in the iris, retina, TG, and BS of mice following ocular infection with HSV–1. Since CXCR3 is predominantly expressed on activated T lymphocytes and NK cells within the immune system, it would appear that these cells may not be essential for viral clearance in the cornea.
Keywords: cytokines/chemokines • herpes simplex virus • inflammation