title: CXCL9 compensates for the absence of CXCL10 during recurrent Herpetic stromal keratitis.
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.
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Deena
authors.initials: D
authors.lastname: Tajfirouz
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Devin M
authors.initials: DM
authors.lastname: West
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Xiao-Tang
authors.initials: XT
authors.lastname: Yin
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Chloe A
authors.initials: CA
authors.lastname: Potter
authors.affiliation: Departments of Medicine, Pathology & Immunology, Anatomy & Neurobiology Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Robyn
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA. Electronic address: pstuart2@slu.edu.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Stuart
mesh_terms: D000818:Animals; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism / Q000821:virology; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016849:Keratitis, Herpetic / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D051379:Mice; D015854:Up-Regulation
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9
keywords: CXCL10; CXCL9; Chemokines; Cornea; Herpes simplex virus type 1; Herpetic stromal keratitis; Inflammation