title: On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis.
abstract: Corneal infection with herpes simplex virus-1 in immunocompetent mice induces an immunopathologic response termed herpetic stromal keratitis (HSK). The earliest sign of disease is neutrophil infiltration, which lasts for 48 to 72 h and then disappears. However, a secondary neutrophil infiltration, this time more massive, occurs, beginning 8 to 9 days postinfection, a time in which HSK becomes clinically evident. The role of neutrophils in HSK expression was investigated by eliminating such cells using a specific mAb (RB6-8C5). In neutrophil-depleted immunocompetent mice, virus replicated more abundantly, but no effects on HSK expression were observed, possibly because sustained neutropenia could not be maintained. However, using a severe combined immunodeficient mouse model, in which HSK does not occur unless given adoptive transfer of CD4+ T cells, the effects of neutrophil depletion were more pronounced. There were significantly less incidence and severity of HSK in CD4+ T cell-reconstituted severe combined immunodeficient mice that were depleted of neutrophils as compared with controls. Neutrophil-depleted mice displayed moderate to severe periocular skin lesions, progressively became cachetic, and developed signs of encephalitis. Virus was recovered at higher titers and for longer periods from eyes of neutrophil-depleted animals. Brain virus titers were also significantly higher on day 12 postinfection as compared with control animals. These results suggest that herpes simplex virus infection of the cornea rapidly invokes recruitment of neutrophils that may aid in viral clearance, and that neutrophils directly or indirectly serve as agonists in perpetuating a CD4+ T cell-mediated inflammatory reaction.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Gangappa
authors.forename: S
authors.initials: S
authors.lastname: Kanangat
authors.forename: B T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003315:Cornea / Q000276:immunology / Q000473:pathology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology; D007116:Immunization, Passive; D007156:Immunologic Memory; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology*
chemical_list: D000956:Antigens, Viral