Effect of anti-CXCL10 monoclonal antibody on herpes simplex virus type 1 keratitis and retinal infection.
The inflammatory response to acute ocular herpes simplex virus type 1 (HSV-1) infection in mice involves the innate and adaptive immune response, with an associated increase in the secretion of chemokines, including CXCL10 (interferon-inducible protein 10 kDa [IP-10]). Neutralizing antibodies to mouse CXCL10 were used to determine the role of CXCL10 during the acute phase of HSV-1 ocular infection. Treatment of HSV-1-infected mice with antibody to CXCL10 significantly reduced CXCL10 levels in the eye and trigeminal ganglion and reduced mononuclear cell infiltration into the corneal stroma. These results coincided with reduced ICAM-1 and CXCR3 transcript expression, macrophage inflammatory protein-1alpha and CXCL10 levels, and corneal pathology but increased viral titers in the stroma and trigeminal ganglion. Progression of the virus from the corneal stroma to the retina during acute infection was significantly hindered in anti-CXCL10-treated mice. In addition, colocalization of viral antigen with infiltrating leukocytes in the iris and retina during acute infection suggests that one means by which HSV-1 traffics to the retina involves inflammatory cells (primarily CD11b(+) cells). Collectively, the results suggest that CXCL10 expression in the eye initially orchestrates the inflammatory response to acute HSV-1 infection, which facilitates the spread of the virus to other restricted sites within the eye.
Carr
Daniel J J
DJ
Department of Ophthalmology, Dean A. McGee Eye Institute, The University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Chodosh
James
J
Ash
John
J
Lane
Thomas E
TE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000956:Antigens, Viral / Q000032:analysis; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000502:physiology*; D003315:Cornea / Q000473:pathology; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000628:therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D012160:Retina / Q000821:virology; D012164:Retinal Diseases / Q000628:therapy*; D012668:Trigeminal Ganglion / Q000473:pathology / Q000821:virology; D014779:Virus Replication; D014822:Vitreous Body / Q000821:virology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D054357:Chemokine CXCL10; D019743:Chemokines, CXC