title: IL-17 receptor signaling influences virus-induced corneal inflammation.
abstract: IL-17 has been associated with selected inflammatory and autoimmune diseases. We characterized the expression of this proinflammatory cytokine following HSV-1 corneal infection and investigated whether IL-17R signaling modulated the host response to the viral pathogen at early time-points postinfection. IL-17 was elevated in the murine cornea 24 h after high-dose virus infection and subsequently persisted at low levels during the first week. Immunofluorescent studies showed that the IL-17R was expressed by cultured mouse corneal fibroblasts. Exposure of corneal cells to IL-17 led to production of IL-6 and MIP-2 in vitro and in vivo, indicating that the IL-17R was functional. Mice lacking IL-17R displayed significantly reduced neutrophil infiltration and corneal opacity. However, this effect was transient, as corneal pathology and neutrophil influx resembled that of wild-type (WT) hosts 4 days postinfection. HSV-1 growth and clearance in IL-17R(-/-) hosts were similar to that of the WT controls. Infection of IFN-gamma gene knockout mice was associated with elevated IL-17 levels and accelerated corneal opacity, suggesting that IFN-gamma negatively regulated IL-17 expression. Collectively, our results establish that IL-17 is rapidly produced in the cornea after HSV-1 infection and is regulated at least in part by IFN-gamma. The absence of IL-17 signaling results in a transient decrease in the expression of proinflammatory mediators, neutrophil migration, and corneal pathology, but control of virus growth in the cornea and trigeminal ganglia is not compromised. Thus, IL-17 actively influences early virus-induced corneal inflammation.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA. rlausch@jaguar1.usouthal.edu.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Molesworth-Kenyon
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.forename: John E
authors.initials: JE
authors.lastname: Oakes
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lausch
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism / Q000821:virology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003315:Cornea / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D053582:Interleukin-1alpha / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016849:Keratitis, Herpetic / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053582:Interleukin-1alpha; D015850:Interleukin-6; D053722:Receptors, Interleukin-17; D007371:Interferon-gamma