Abnormal immune response of CCR5-deficient mice to ocular infection with herpes simplex virus type 1.

Abstract

Ocular herpes simplex virus type 1 (HSV-1) infection elicits a strong inflammatory response that is associated with production of the beta chemokines CCL3 and CCL5, which share a common receptor, CCR5. To gain insight into the role of these molecules in ocular immune responses, the corneas of wild-type (WT) and CCR5-deficient (CCR5-/-) mice were infected with HSV-1 and inflammatory parameters were measured. In the absence of CCR5, the early infiltration of neutrophils into the cornea was diminished. Associated with this aberrant leukocyte recruitment, neutrophils in CCR5-/- mice were restricted to the stroma, whereas in WT mice, these cells trafficked to the stroma and epithelial layers of the infected cornea. Virus titres and cytokine/chemokine levels in the infected tissue of these mice were similar for the first 5 days after infection. However, by day 7 post-infection, the CCR5-/- mice showed a significant elevation in the chemokines CCL2, CCL5, CXCL9 and CXCL10 in the trigeminal ganglion and brainstem, as well as a significant increase in virus burden. The increase in chemokine expression was associated with an increase in the infiltration of CD4 and/or CD8 T cells into the trigeminal ganglion and brainstem of CCR5-/- mice. Surprisingly, even though infected CCR5-/- mice were less efficient at controlling the progression of virus replication, there was no difference in mortality. These results suggest that, although CCR5 plays a role in regulating leukocyte trafficking and control of virus burden, compensatory mechanisms are involved in preventing mortality following HSV-1 infection.

• Authors: Daniel J J Carr, John Ash, Thomas E Lane, William A Kuziel
• Journal: The Journal of general virology (J Gen Virol) Vol. 87 Issue Pt 3 Pg. 489-499 (Mar 2006) ISSN: 0022-1317 [Print] England
• PMID: 16476970 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Receptors, CCR5

Topics

• Animals
• Brain Stem (immunology, virology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Count
• Cell Movement
• Chemokines (biosynthesis)
• Chlorocebus aethiops
• Cornea (immunology, virology)
• Herpesvirus 1, Human
• Keratitis, Herpetic (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (physiology)
• Receptors, CCR5 (deficiency, genetics)
• Trigeminal Ganglion (immunology, virology)
• Vero Cells