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Updated: Mar 6, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
CXCL9 compensates for the absence of CXCL10 during recurrent Herpetic stromal keratitis
Deena Tajfirouz1, Devin M West1, Xiao-Tang Yin1
1Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.
Insights
Herpetic stromal keratitis (HSK) is worsened by CXCL10, but CXCL9 compensates when CXCL10 is absent. Neutralizing CXCL9 reduced disease in mice lacking CXCL10, highlighting chemokine roles in HSK pathogenesis.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Background:
- Herpetic stromal keratitis (HSK) is a corneal disease often caused by herpes simplex virus type 1 (HSV-1) reactivation.
- Chemokines, such as CXCL10, play a role in recruiting immune cells to the cornea during HSK.
- The precise roles of specific chemokines in HSK pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the specific roles of CXCL10 and CXCL9 in the pathogenesis of HSV-1-induced HSK.
- To determine if CXCL9 expression compensates for the absence of CXCL10 during HSK.
Main Methods:
- Utilized B6-CXCL10-/- mice and wild-type (B6) mice infected with HSV-1.
- Measured CXCL9 and CXCL10 expression levels in infected corneas.
- Administered neutralizing antibodies against CXCL9 to assess disease severity.
Main Results:
- Neutralizing CXCL10 reduced HSK severity in wild-type mice.
- Mice lacking CXCL10 (B6-CXCL10-/-) exhibited exacerbated HSK.
- CXCL9 expression was significantly upregulated in B6-CXCL10-/- mice compared to B6 mice.
- Neutralizing CXCL9 ameliorated HSK in B6-CXCL10-/- mice but not in B6 mice.
Conclusions:
- CXCL10 contributes to the worsening of HSK.
- CXCL9 acts as a compensatory mechanism in the absence of CXCL10, influencing HSK severity.
- Targeting CXCL10 and understanding CXCL9's compensatory role are crucial for managing recurrent HSK.
Abstract:
Herpetic stromal keratitis (HSK) is a disease that is typically associated with reactivation of a latent HSV-1 infection. This disease is driven, in part, by chemokines that recruit leukocytes to the cornea. Surprisingly, neutralization of CXCL10 significantly reduced disease, while B6-CXCL10-/- mice exhibited worse disease compared with similarly infected wild-type controls. We hypothesized that compensatory up-regulation of CXCL9 occurs in the absence of CXCL10. Analysis of CXCL9 expression in HSV-1-infected B6 mice and B6-CXCL10-/- mice revealed significantly more CXCL9 in B6-XCL10-/- mice. Treatment of B6 and B6-CXCL10-/- mice with neutralizing antibodies to CXCL9 reduced HSK scores in B6-CXCL10-/-, but not B6 mice. We conclude that CXCL10 production worsens HSK and that CXCL9 may compensate in CXCL10-deficient animals. These studies identify the critical role that CXCL10 plays in the pathogenesis of recurrent HSK, and that CXCL9 displays its importance when CXCL10 is absent.
