title: Absence of CXCL10 aggravates herpes stromal keratitis with reduced primary neutrophil influx in mice.
abstract: Herpes simplex virus 1 (HSV-1) replication initiates inflammation and angiogenesis responses in the cornea to result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced vision impairment. Chemokines are secreted to modulate HSK by recruiting leukocytes, which affect virus growth, and by influencing angiogenesis. The present study used a murine infection model to investigate the significance of the chemokine CXC chemokine ligand 10 (CXCL10; gamma interferon-inducible protein 10 [IP-10]) in HSK. Here, we show that HSV-1 infection of the cornea induced CXCL10 protein expression in epithelial cells. The corneas of mice with a targeted disruption of the gene encoding CXCL10 displayed decreases in levels of neutrophil-attracting cytokine (interleukin-6), primary neutrophil influx, and viral clearance 2 or 3 days postinfection. Subsequently, absence of CXCL10 aggravated HSK with elevated levels of interleukin-6, chemokines for CD4(+) T cells and/or neutrophils (macrophage inflammatory protein-1α and macrophage inflammatory protein-2), angiogenic factor (vascular endothelial growth factor A), and secondary neutrophil influx, as well as infiltration of CD4(+) T cells to exacerbate opacity and angiogenesis in the cornea at 14 and up to 28 days postinfection. Our results collectively show that endogenous CXCL10 contributes to recruit the primary neutrophil influx and to affect the expression of cytokines, chemokines, and angiogenic factors as well as to reduce the viral titer and HSK severity.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Taiwan, Republic of China.
authors.forename: Fang-Hsiu
authors.initials: FH
authors.lastname: Shen
authors.forename: Shainn-Wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
authors.forename: Yuk-Ying
authors.initials: YY
authors.lastname: Tung
authors.forename: Sheng-Min
authors.initials: SM
authors.lastname: Hsu
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054357:Chemokine CXCL10 / Q000172:deficiency* / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D003315:Cornea / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D013997:Time Factors
chemical_list: D054357:Chemokine CXCL10; D018925:Chemokines; C485433:Cxcl10 protein, mouse