CXCL9 compensates for the absence of CXCL10 during recurrent Herpetic stromal keratitis

• Published in: Virology (New York, N.Y.) N.Y.), 2017-06, Vol.506, p.7-13
• Main Authors: Tajfirouz, Deena, West, Devin M, Yin, Xiao-Tang, Potter, Chloe A, Klein, Robyn, Stuart, Patrick M
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Chemokine CXCL9 - genetics; Chemokine CXCL9 - metabolism; Chemokines; Cornea; Cornea - metabolism; Cornea - virology; CXCL10; CXCL9; Female; Herpes simplex virus type 1; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - physiology; Herpetic stromal keratitis; Humans; Infectious Disease; Inflammation; Keratitis, Herpetic - genetics; Keratitis, Herpetic - metabolism; Keratitis, Herpetic - virology; Mice; Up-Regulation
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2017.02.022

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.