Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids.
Herpetic stromal keratitis (HSK) and blepharoconjunctivitis in humans are thought partly to result from immunopathological responses to herpes simplex virus type 1 (HSV-1). The corneas of NIH mice were inoculated with HSV-1 (strain McKrae) and mice were examined for signs of disease and infection on days 1, 4, 7, 10, 14 and 21. The eyes and eyelids of infected and control mice were processed for immunohistochemistry and double stained for viral antigens and one of the following cell surface markers (Gr-1, F4/80, CD4, CD8, CD45R or MHC class II) or one of the following cytokines (IL-2, IL-4, IL-6, IL-10, IL-12 or IFN-gamma). All infected mice developed signs of HSK by day 4 and blepharitis by day 7 and these both persisted until day 21, when signs of resolution where apparent. Virus was detected during the first week of infection and became undetectable by day 10. Large numbers of Gr-1(+) cells (neutrophils) infiltrated infected corneas and eyelids in areas of viral antigen and CD4(+) T cells increased significantly in number after virus clearance. In both sites, the predominant cytokines were IL-6, IL-10, IL-12 and IFN-gamma, with few IL-2(+) and IL-4(+) cells. These observations suggest that the immune responses in the cornea are similar to those in the eyelids but, overall, the responses are not clearly characterized as either Th1 or Th2. In both sites, the neutrophil is the predominant infiltrating cell type and is a likely source of the cytokines observed and a major effector of the disease process.
Stumpf
Thomas H
TH
Division of Ophthalmology1 and Department of Pathology and Microbiology2, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Case
Rachel
R
Division of Ophthalmology1 and Department of Pathology and Microbiology2, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Shimeld
Carolyn
C
Division of Ophthalmology1 and Department of Pathology and Microbiology2, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Easty
David L
DL
Division of Ophthalmology1 and Department of Pathology and Microbiology2, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Hill
Terry J
TJ
Division of Ophthalmology1 and Department of Pathology and Microbiology2, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001762:Blepharitis / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D003231:Conjunctivitis / Q000276:immunology / Q000821:virology; D003315:Cornea / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005143:Eyelids / Q000276:immunology* / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000276:immunology / Q000821:virology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000276:immunology; D013997:Time Factors
D000956:Antigens, Viral; D016207:Cytokines