Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection.

Abstract

The chemokine, CXCL10, chemotactic for NK cells, activated T cells, and dendritic cells is highly expressed during viral infections, including HSV-1. The importance of this chemokine to the control of HSV-1 infection was tested using mice deficient in CXCL10 (CXCL10(-/-)). Following corneal infection, HSV-1 viral titers were elevated in the nervous system of CXCL10(-/-) mice, which correlated with defects in leukocyte recruitment including dendritic cells, NK cells, and HSV-1-specific CD8(+) T cells to the brain stem. In the absence of NK cells and HSV-1-specific CD8(+) T cells in wild-type (WT) or CXCL10(-/-) mice, similar levels of virus were recovered in the nervous system, suggesting these cells are responsible for the observed defects in the control of viral replication in CXCL10(-/-) mice. Leukocyte mobilization was also compared between WT, CXCL10(-/-), and mice deficient in the only known receptor for CXCL10, CXCR3 (CXCR3 (-/-)). NK cell mobilization was comparably reduced in both CXCL10(-/-) and CXCR3(-/-) mice relative to WT animals. However, the reduction in mobilization of HSV-1-specific CD8(+) T cells in CXCL10(-/-) was not observed in CXCR3(-/-) mice following HSV-1 infection. The defect was not the result of an alternative receptor for CXCL10, as Ag-specific CD8(+) T cell recruitment was not reduced in mice which were deficient in both CXCL10 and CXCR3. Thus, CXCL10 deficiency results in reduced mobilization of HSV-1-specific CD8(+) T cells as a result of dysregulation of CXCR3 signaling.

• Authors: Todd R Wuest, Daniel J J Carr
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 11 Pg. 7985-93 (Dec 01 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 19017990 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Chemokine CXCL10
• Cxcl10 protein, mouse
• Cxcr3 protein, mouse
• Receptors, CXCR3

Topics

• Animals
• Antigens, Viral (genetics, immunology)
• Brain Stem (immunology, virology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Movement (genetics, immunology)
• Chemokine CXCL10 (genetics, immunology)
• Corneal Diseases (genetics, immunology, virology)
• Dendritic Cells (immunology)
• Gene Expression Regulation (genetics, immunology)
• Herpes Simplex (genetics, immunology)
• Herpesvirus 1, Human (immunology)
• Killer Cells, Natural (immunology)
• Mice
• Mice, Knockout
• Receptors, CXCR3 (genetics, immunology)
• Signal Transduction (genetics, immunology)