摘要
Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
基金
supported by USPHS grant (No. AI053108) to DanielJ.J. Carr
P20 (No. RR017703)
an unrestricted grant from Research to Prevent Blindness
supported by NIAID training grant(No. AI007633)