1887

Journal of General Virology header logo

Volume 83, Issue 7

Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids Free

Abstract

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-γ). 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-γ, 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.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-7-1579
2002-07-01
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/7/0831579a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-7-1579&mimeType=html&fmt=ahah

References

  1. Avery A. C., Zhao Z. S., Rodriguez A., Bikoff E. K., Soheilian M., Foster C. S., Cantor H. 1995; Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide. Nature 376:431–434
     [Google Scholar]
  2. Babu J. S., Kanangat S., Rouse B. T. 1995; T cell cytokine mRNA expression during the course of the immunopathologic ocular disease herpetic stromal keratitis. Journal of Immunology 154:4822–4829
     [Google Scholar]
  3. Biron C. A. 1998; Role of early cytokines, including α and β interferons (IFN-α/β), in innate and adaptive immune responses to viral infections. Seminars in Immunology 10:383–390
     [Google Scholar]
  4. Chen W., Tang Q., Hendricks R. L. 1996; Ex vivo model of leukocyte migration into herpes simplex virus-infected mouse corneas. Journal of Leukocyte Biology 60:167–173
     [Google Scholar]
  5. Chun S., Daheshia M., Kuklin N. A., Rouse B. T. 1998; Modulation of viral immunoinflammatory responses with cytokine DNA administered by different routes. Journal of Virology 72:5545–5551
     [Google Scholar]
  6. Daheshia M., Kanangat S., Rouse B. T. 1998; Production of key molecules by ocular neutrophils early after herpetic infection of the cornea. Experimental Eye Research 67:619–624
     [Google Scholar]
  7. Dennis R. F., Siemasko K. F., Tang Q., Hendricks R. L., Finnegan A. 1995; Involvement of LFA-1 and ICAM-1 in the herpetic disease resulting from HSV-1 corneal infection. Current Eye Research 14:55–62
     [Google Scholar]
  8. di Giovine F. S., Mee J. B., Duff G. W. 1996; Immunoregulatory cytokines. In Therapeutic Modulation of Cytokines pp 37–65 Edited by Henderson B., Bodmer M. W. London: CRC Press;
     [Google Scholar]
  9. Egerer I., Stary A. 1980; Erosive-ulcerative herpes simplex blepharitis. Archives of Ophthalmology 98:1760–1763
     [Google Scholar]
  10. Gangappa S., Deshpande S. P., Rouse B. T. 2000; Bystander activation of CD4+ T cells accounts for herpetic ocular lesions. Investigative Ophthalmology & Visual Science 41:453–459
     [Google Scholar]
  11. Ghiasi H., Wechsler S. L., Kaiwar R., Nesburn A. B., Hofman F. M. 1995; Local expression of tumor necrosis factor α and interleukin-2 correlates with protection against corneal scarring after ocular challenge of vaccinated mice with herpes simplex virus type 1. Journal of Virology 69:334–340
     [Google Scholar]
  12. Hansch G. M., Radsak M., Wagner C., Reis B., Koch A., Breitbart A., Andrassy K. 1999; Expression of major histocompatibility class II antigens on polymorphonuclear neutrophils in patients with Wegener’s granulomatosis. Kidney International 55:1811–1818
     [Google Scholar]
  13. Hendricks R. L. 1999; Immunopathogenesis of viral ocular infections. Chemical Immunology 73:120–136
     [Google Scholar]
  14. Hendricks R. L., Tumpey T. M. 1991; Concurrent regeneration of T lymphocytes and susceptibility to HSV-1 corneal stromal disease. Current Eye Research 10:47–53
     [Google Scholar]
  15. Hendricks R. L., Tumpey T. M., Finnegan A. 1992; IFN-γ and IL-2 are protective in the skin but pathologic in the corneas of HSV-1-infected mice. Journal of Immunology 149:3023–3028
     [Google Scholar]
  16. Inoue T., Inoue Y., Kosaki R., Nishida K., Shimomura Y., Tano Y., Hayashi K. 2001; Immunohistological study of infiltrated cells and cytokines in murine herpetic keratitis. Acta Ophthalmologica Scandinavica 79:484–487
     [Google Scholar]
  17. Jayaraman S., Heiligenhaus A., Rodriguez A., Soukiasian S., Dorf M. E., Foster C. S. 1993; Exacerbation of murine herpes simplex virus-mediated stromal keratitis by Th2 type T cells. Journal of Immunology 151:5777–5789
     [Google Scholar]
  18. Kanangat S., Thomas J., Gangappa S., Babu J. S., Rouse B. T. 1996; Herpes simplex virus type 1-mediated up-regulation of IL-12 (p40) mRNA expression. Implications in immunopathogenesis and protection. Journal of Immunology 156:1110–1116
     [Google Scholar]
  19. Liesegang T. J. 1989; Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Archives of Ophthalmology 107:1160–1165
     [Google Scholar]
  20. Maggs D. J., Chang E., Nasisse M. P., Mitchell W. J. 1998; Persistence of herpes simplex virus type 1 DNA in chronic conjunctival and eyelid lesions of mice. Journal of Virology 72:9166–9172
     [Google Scholar]
  21. Metcalf J. F., Hamilton D. S., Reichert R. W. 1979; Herpetic keratitis in athymic (nude) mice. Infection and Immunity 26:1164–1171
     [Google Scholar]
  22. Miller J. K., Laycock K. A., Umphress J. A., Hook K. K., Stuart P. M., Pepose J. S. 1996; A comparison of recurrent and primary herpes simplex keratitis in NIH inbred mice. Cornea 15:497–504
     [Google Scholar]
  23. Niemialtowski M. G., Rouse B. T. 1992; Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis. Journal of Immunology 149:3035–3039
     [Google Scholar]
  24. Radsak M., Iking-Konert C., Stegmaier S., Andrassy K., Hansch G. M. 2000; Polymorphonuclear neutrophils as accessory cells for T-cell activation: major histocompatibility complex class II restricted antigen-dependent induction of T-cell proliferation. Immunology 101:521–530
     [Google Scholar]
  25. Romani L., Mencacci A., Cenci E., Del Sero G., Bistoni F., Puccetti P. 1997; An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis. Journal of Immunology 158:2356–2362
     [Google Scholar]
  26. Russell R. G., Nasisse M. P., Larsen H. S., Rouse B. T. 1984; Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Investigative Ophthalmology & Visual Science 25:938–944
     [Google Scholar]
  27. Shimeld C., Hill T. J., Blyth W. A., Easty D. L. 1990a; Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system. Journal of General Virology 71:681–687
     [Google Scholar]
  28. Shimeld C., Hill T. J., Blyth W. A., Easty D. L. 1990b; Reactivation of latent infection and induction of recurrent herpetic eye disease in mice. Journal of General Virology 71:397–404
     [Google Scholar]
  29. Shimeld C., Whiteland J. L., Nicholls S. M., Grinfeld E., Easty D. L., Gao H., Hill T. J. 1995; Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1. Journal of Neuroimmunology 61:7–16
     [Google Scholar]
  30. Shimeld C., Whiteland J. L., Nicholls S. M., Easty D. L., Hill T. J. 1996; Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease. Journal of General Virology 77:977–985
     [Google Scholar]
  31. Shimeld C., Whiteland J. L., Williams N. A., Easty D. L., Hill T. J. 1997; Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1. Journal of General Virology 78:3317–3325
     [Google Scholar]
  32. Shimeld C., Efstathiou S., Hill T. 2001; Tracking the spread of a lacZ-tagged herpes simplex virus type 1 between the eye and the nervous system of the mouse: comparison of primary and recurrent infection. Journal of Virology 75:5252–5262
     [Google Scholar]
  33. Smith T. J., Ackland-Berglund C. E., Leib D. A. 2000; Herpes simplex virus virion host shutoff (vhs) activity alters periocular disease in mice. Journal of Virology 74:3598–3604
     [Google Scholar]
  34. Stumpf T. H., Shimeld C., Easty D. L., Hill T. J. 2001; Cytokine production in a murine model of recurrent herpetic stromal keratitis. Investigative Ophthalmology & Visual Science 42:372–378
     [Google Scholar]
  35. Summers B. C., Margolis T. P., Leib D. A. 2001; Herpes simplex virus type 1 corneal infection results in periocular disease by zosteriform spread. Journal of Virology 75:5069–5075
     [Google Scholar]
  36. Tang Q., Chen W., Hendricks R. L. 1997; Proinflammatory functions of IL-2 in herpes simplex virus corneal infection. Journal of Immunology 158:1275–1283
     [Google Scholar]
  37. Thomas J., Gangappa S., Kanangat S., Rouse B. T. 1997; On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis. Journal of Immunology 158:1383–1391
     [Google Scholar]
  38. Tullo A. B., Shimeld C., Blyth W. A., Hill T. J., Easty D. L. 1983; Ocular infection with herpes simplex virus in nonimmune and immune mice. Archives of Ophthalmology 101:961–964
     [Google Scholar]
  39. Tumpey T. M., Elner V. M., Chen S. H., Oakes J. E., Lausch R. N. 1994; Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1. Journal of Immunology 153:2258–2265
     [Google Scholar]
  40. Tumpey T. M., Cheng H., Yan X. T., Oakes J. E., Lausch R. N. 1998; Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10. Journal of Leukocyte Biology 63:486–492
     [Google Scholar]
  41. Whiteland J. L., Nicholls S. M., Shimeld C., Easty D. L., Williams N. A., Hill T. J. 1995; Immunohistochemical detection of T-cell subsets and other leukocytes in paraffin-embedded rat and mouse tissues with monoclonal antibodies. Journal of Histochemistry and Cytochemistry 43:313–320
     [Google Scholar]
  42. Whiteland J. L., Shimeld C., Nicholls S. M., Easty D. L., Williams N. A., Hill T. J. 1997; Immunohistochemical detection of cytokines in paraffin-embedded mouse tissues. Journal of Immunological Methods 210:103–108
     [Google Scholar]
  43. Yeaman G. R., Collins J. E., Currie J. K., Guyre P. M., Wira C. R., Fanger M. W. 1998; IFN-γ is produced by polymorphonuclear neutrophils in human uterine endometrium and by cultured peripheral blood polymorphonuclear neutrophils. Journal of Immunology 160:5145–5153
     [Google Scholar]
  44. Zhao Z. S., Granucci F., Yeh L., Schaffer P. A., Cantor H. 1998; Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 279:1344–1347
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-7-1579
Loading
Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids
J. Gen. Virol. 83, 1579 (2002); https://doi.org/10.1099/0022-1317-83-7-1579
/content/journal/jgv/10.1099/0022-1317-83-7-1579
/content/journal/jgv/10.1099/0022-1317-83-7-1579
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error