Abnormal immune response of CCR5-deficient mice to ocular infection with herpes simplex virus type 1.
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.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, DMEI #415, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Department of Ophthalmology, University of Oklahoma Health Sciences Center, DMEI #415, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Daniel J J
DJJ
Carr
Department of Ophthalmology, University of Oklahoma Health Sciences Center, DMEI #415, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
John
J
Ash
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, DMEI #415, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Thomas E
TE
Lane
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92037, USA.
William A
WA
Kuziel
D000818:Animals; D001933:Brain Stem / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D003315:Cornea / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics; D012668:Trigeminal Ganglion / Q000276:immunology / Q000821:virology; D014709:Vero Cells
D018925:Chemokines; D019713:Receptors, CCR5