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

• DOI: 10.1099/vir.0.81339-0
• Publication Date: 2006-02-13T21:58:34Z
• Authors: Daniel J. J. Carr; John Ash; Thomas E. Lane; William A. Kuziel
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; 0303 health sciences; Receptors, CCR5; Neutrophils; Cell Count; Herpesvirus 1, Human; CD8-Positive T-Lymphocytes; 3. Good health; Cornea; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Trigeminal Ganglion; Cell Movement; Chlorocebus aethiops; Keratitis, Herpetic; Animals; Chemokines; Vero Cells; Brain Stem

Ocular herpes simplex virus type 1 (HSV-1) infection elicits a strong inflammatory response that is associated with production of theβchemokines 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.