VEGF-A expression by HSV-1-infected cells drives corneal lymphangiogenesis.

Abstract

Inflammatory lymphangiogenesis plays a crucial role in the development of inflammation and transplant rejection. The mechanisms of inflammatory lymphangiogenesis during bacterial infection, toll-like receptor ligand administration, and wound healing are well characterized and depend on ligands for the vascular endothelial grow factor receptor (VEGFR) 3 that are produced by infiltrating macrophages. But inflammatory lymphangiogenesis in nonlymphoid tissues during chronic viral infection is unstudied. Herpes simplex virus 1 (HSV-1) infection of the cornea is a leading cause of blindness and depends on aberrant host immune responses to antigen within the normally immunologically privileged cornea. We report that corneal HSV-1 infection drives lymphangiogenesis and that corneal lymphatics persist past the resolution of infection. The mechanism of HSV-1-induced lymphangiogenesis was distinct from the described mechanisms of inflammatory lymphangiogenesis. HSV-1-elicited lymphangiogenesis was strictly dependent on VEGF-A/VEGFR-2 signaling but not on VEGFR-3 ligands. Macrophages played no role in the induction of lymphangiogenesis and were not a detectable source of VEGF-A. Rather, using VEGF-A reporter transgenic mice, we have identified infected epithelial cells as the primary source of VEGF-A during HSV-1 infection. Our results indicate that HSV-1 directly induces vascularization of the cornea through up-regulation of VEGF-A expression.

• Authors: Todd R Wuest, Daniel J J Carr
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 207 Issue 1 Pg. 101-15 (Jan 18 2010) ISSN: 1540-9538 [Electronic] United States
• PMID: 20026662 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Viral
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Vascular Endothelial Growth Factor Receptor-2
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Animals
• Antigens, Viral (immunology, metabolism)
• Cell Movement (genetics, immunology)
• Cornea (immunology, metabolism, pathology, virology)
• Corneal Neovascularization (genetics, immunology, metabolism, virology)
• Gene Expression Regulation (genetics, immunology)
• Herpes Simplex (genetics, immunology, metabolism, pathology)
• Herpesvirus 1, Human (immunology, metabolism)
• Inflammation (genetics, immunology, metabolism, pathology, virology)
• Lymphatic Vessels (immunology, metabolism, pathology)
• Macrophages (immunology, metabolism, pathology)
• Mice
• Mice, Transgenic
• Signal Transduction (genetics, immunology)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics, immunology)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, immunology, metabolism)
• Vascular Endothelial Growth Factor Receptor-3 (immunology, metabolism)